Journal articles: 'Molecule identification'

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Dührkop, Kai. "Computational methods for small molecule identification." it - Information Technology 61, no. 5-6 (October 25, 2019): 285–92. http://dx.doi.org/10.1515/itit-2019-0033.

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Abstract Identification of small molecules remains a central question in analytical chemistry, in particular for natural product research, metabolomics, environmental research, and biomarker discovery. Mass spectrometry is the predominant technique for high-throughput analysis of small molecules. But it reveals only information about the mass of molecules and, by using tandem mass spectrometry, about the mass of molecular fragments. Automated interpretation of mass spectra is often limited to searching in spectral libraries, such that we can only dereplicate molecules for which we have already recorded reference mass spectra. In my thesis “Computational methods for small molecule identification” we developed SIRIUS, a tool for the structural elucidation of small molecules with tandem mass spectrometry. The method first computes a hypothetical fragmentation tree using combinatorial optimization. By using a Bayesian statistical model, we can learn parameters and hyperparameters of the underlying scoring directly from data. We demonstrate that the statistical model, which was fitted on a small dataset, generalizes well across many different datasets and mass spectrometry instruments. In a second step the fragmentation tree is used to predict a molecular fingerprint using kernel support vector machines. The predicted fingerprint can be searched in a structure database to identify the molecular structure. We demonstrate that our machine learning model outperforms all other methods for this task, including its predecessor FingerID. SIRIUS is available as commandline tool and as user interface. The molecular fingerprint prediction is implemented as web service and receives over one million requests per month.

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Mills, Randell L., William R. Good, and Robert M. Shaubach. "Dihydrino Molecule Identification." Fusion Technology 25, no. 1 (January 1994): 103–19. http://dx.doi.org/10.13182/fst94-a30239.

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Bell, David C., W. Kelley Thomas, Katelyn M. Murtagh, Cheryl A. Dionne, Adam C. Graham, Jobriah E. Anderson, and William R. Glover. "DNA Base Identification by Electron Microscopy." Microscopy and Microanalysis 18, no. 5 (October 2012): 1049–53. http://dx.doi.org/10.1017/s1431927612012615.

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AbstractAdvances in DNA sequencing, based on fluorescent microscopy, have transformed many areas of biological research. However, only relatively short molecules can be sequenced by these technologies. Dramatic improvements in genomic research will require accurate sequencing of long (>10,000 base-pairs), intact DNA molecules. Our approach directly visualizes the sequence of DNA molecules using electron microscopy. This report represents the first identification of DNA base pairs within intact DNA molecules by electron microscopy. By enzymatically incorporating modified bases, which contain atoms of increased atomic number, direct visualization and identification of individually labeled bases within a synthetic 3,272 base-pair DNA molecule and a 7,249 base-pair viral genome have been accomplished. This proof of principle is made possible by the use of a dUTP nucleotide, substituted with a single mercury atom attached to the nitrogenous base. One of these contrast-enhanced, heavy-atom-labeled bases is paired with each adenosine base in the template molecule and then built into a double-stranded DNA molecule by a template-directed DNA polymerase enzyme. This modification is small enough to allow very long molecules with labels at each A-U position. Image contrast is further enhanced by using annular dark-field scanning transmission electron microscopy (ADF-STEM). Further refinements to identify additional base types and more precisely determine the location of identified bases would allow full sequencing of long, intact DNA molecules, significantly improving the pace of complex genomic discoveries.

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LEE, J., H. LI, and E. YEUNG. "Single-molecule spectroscopy for molecular identification in capillary electrophoresis." Journal of Chromatography A 1053, no. 1-2 (October 22, 2004): 173–79. http://dx.doi.org/10.1016/s0021-9673(04)01091-x.

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Li, Qingxin, and CongBao Kang. "Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery." International Journal of Molecular Sciences 21, no. 15 (July 24, 2020): 5262. http://dx.doi.org/10.3390/ijms21155262.

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Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins. These compounds have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. A target-based drug discovery project usually includes target identification, target validation, hit identification, hit to lead and lead optimization. Understanding molecular interactions between small molecules and their targets is critical in drug discovery. Although many biophysical and biochemical methods are able to elucidate molecular interactions of small molecules with their targets, structural biology is the most powerful tool to determine the mechanisms of action for both targets and the developed compounds. Herein, we reviewed the application of structural biology to investigate binding modes of orthosteric and allosteric inhibitors. It is exemplified that structural biology provides a clear view of the binding modes of protease inhibitors and phosphatase inhibitors. We also demonstrate that structural biology provides insights into the function of a target and identifies a druggable site for rational drug design.

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Jing, Nan, Jun Kameoka, Chin B. Su, Chao-Kai Chou, and Mien-Chie Hung. "Nanofluidic Devices for Single Molecule Identification." Journal of Photopolymer Science and Technology 21, no. 4 (2008): 531–36. http://dx.doi.org/10.2494/photopolymer.21.531.

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Flower, Darren R. "Systematic identification of small molecule adjuvants." Expert Opinion on Drug Discovery 7, no. 9 (June 24, 2012): 807–17. http://dx.doi.org/10.1517/17460441.2012.699958.

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Ding, Fangyuan, Maria Manosas, Michelle M. Spiering, Stephen J. Benkovic, David Bensimon, Jean-François Allemand, and Vincent Croquette. "Single-molecule mechanical identification and sequencing." Nature Methods 9, no. 4 (March 11, 2012): 367–72. http://dx.doi.org/10.1038/nmeth.1925.

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Chauhan, Ritika, Vinita Chauhan, Priyanka Sonkar, and Ram Kumar Dhaked. "Identification of Inhibitors against Botulinum Neurotoxins: 8-Hydroxyquinolines Hold Promise." Mini-Reviews in Medicinal Chemistry 19, no. 20 (December 16, 2019): 1694–706. http://dx.doi.org/10.2174/1389557519666190906120228.

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Botulinum neurotoxins (BoNTs) are the most toxic category A biological warfare agents. There is no therapeutics available for BoNT intoxication yet, necessitating the development of a medical countermeasure against these neurotoxins. The discovery of small molecule-based drugs has revolutionized in the last two decades resulting in the identification of several small molecule inhibitors of BoNTs. However, none progressed to clinical trials. 8-Hydroxyquinolines scaffold-based molecules are important ‘privileged structures’ that can be exploited as inhibitors of a diverse range of targets. In this review, our study of recent reports suggests the development of 8-hydroxyquinoline derived molecules as a potential drug may be on the horizon.

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ANTONOPOULOU, Smaragdi, A. Constantinos DEMOPOULOS, Dimitris ARGYROPOULOS, George BALTAS, Helen KOTSIFAKI, and Anthoula DIAMANTI-KIPIOTI. "Identification of a new endogenous platelet-activating factor-like molecule in gingival crevicular fluid." Biochemical Journal 330, no. 2 (March 1, 1998): 791–94. http://dx.doi.org/10.1042/bj3300791.

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Periodontal disease is an inflammatory disease and the major cause of tooth loss in adults. Bacteria and their products are the causative agents of this disease. Endogenous molecules mediate the inflammatory process and play a major role in its amplification and perpetuation as well as in the ensuing tissue destruction. The relationship between platelet-activating factor (PAF) and periodontal disease has not so far been examined thoroughly. We have isolated a phospholipid molecule with PAF-like activity from gingival crevicular fluid. This molecule, purified on HPLC, causes washed platelet aggregation with EC50 value 0.1 μM, based on phosphorus determination. It acts through PAF-receptors and is inactivated by PAF-acetylhydrolase. In addition, this phospholipid presents biological activity towards human platelets. The combination of the results obtained from the chemical and enzymic treatments, the biological assays as well as results from the electrospray analysis, leads to the conclusion that this phospholipid is a hydroxyl-PAF analogue with relative molecular mass 703. This PAF-like molecule may be implicated in periodontal disease.

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Ramos, Ryan, Josivan Costa, Rai Silva, Glauber da Costa, Alex Rodrigues, Érica Rabelo, Raimundo Souto, et al. "Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening." Pharmaceuticals 12, no. 1 (January 25, 2019): 20. http://dx.doi.org/10.3390/ph12010020.

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Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against Ae. aegypti via virtual screening. Pyriproxyfen was chosen as a template compound to search molecules in the database Zinc_Natural_Stock (ZNSt) with structural similarity using ROCS (rapid overlay of chemical structures) and EON (electrostatic similarity) software, and in the final search, the top 100 were selected. Subsequently, in silico pharmacokinetic and toxicological properties were determined resulting in a total of 14 molecules, and these were submitted to the PASS online server for the prediction of biological insecticide and acetylcholinesterase activities, and only two selected molecules followed for the molecular docking study to evaluate the binding free energy and interaction mode. After these procedures were performed, toxicity risk assessment such as LD50 values in mg/kg and toxicity class using the PROTOX online server, were undertaken. Molecule ZINC00001624 presented potential for inhibition for the acetylcholinesterase enzyme (insect and human) with a binding affinity value of −10.5 and −10.3 kcal/mol, respectively. The interaction with the juvenile hormone was −11.4 kcal/mol for the molecule ZINC00001021. Molecules ZINC00001021 and ZINC00001624 had excellent predictions in all the steps of the study and may be indicated as the most promising molecules resulting from the virtual screening of new insecticidal agents.

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Latchman, Yvette, Paul F. McKay, and Hans Reiser. "Cutting Edge: Identification of the 2B4 Molecule as a Counter-Receptor for CD48." Journal of Immunology 161, no. 11 (December 1, 1998): 5809–12. http://dx.doi.org/10.4049/jimmunol.161.11.5809.

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Abstract The CD48 molecule belongs to a subfamily of the Ig superfamily that also includes the CD2, CD58, 2B4, Signaling lymphocyte activation molecule (SLAM), and Ly-9 molecules. Receptor-ligand interactions are known to occur between several members of this family, and these interactions can strengthen cell to cell adhesion. In mice, the CD48 molecule can bind to CD2. To search for additional ligands of murine CD48, we have generated a chimeric fusion protein consisting of the extracellular domain of murine CD48 and the C region of human IgG1. The results of immunofluorescence and immunoprecipitation experiments in which this reagent was used identify the 2B4 molecule as a novel counter-receptor of CD48.

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Li, Chunshen, Yingying Shi, Lihua Zuo, Mingzhe Xin, Xiaomeng Guo, Jianli Sun, Shuai Chen, et al. "Identification of Biomarkers Associated with Cancerous Change in Oral Leukoplakia Based on Integrated Transcriptome Analysis." Journal of Oncology 2022 (January 19, 2022): 1–22. http://dx.doi.org/10.1155/2022/4599305.

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Objective. Oral leukoplakia (OLK) is the most common precancerous lesion in the oral cavity. This study aimed to explore key biomarkers for monitoring OLK for early diagnosis of oral squamous cell carcinoma (OSCC) and screen small-molecule drugs for the prevention of OSCC. Method. The Gene Expression Omnibus (GEO) database was explored to extract two microarray datasets, namely, GSE85195 and GSE25099. The data of the normal group, OLK group, and OSCC group were analyzed by weighted gene coexpression network analysis (WGCNA) to identify the most significant gene module and differentially expressed genes (DEGs). The intersection genes were extracted as the key genes of OLK carcinogenesis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed in the module. Connectivity Map and molecular docking were used to screen small-molecule drugs. The diagnostic values of four key genes were identified and verified in the GSE26549 dataset. Results. WGCNA obtained the red module (r = −0.91, p < 0.05 ) with the strongest correlation with cancerous phenotype. GO enrichment analysis showed 60 pathways, including 28 biological processes, 11 cell components, and 21 molecular functions, and KEGG enrichment analysis showed 4 pathways ( p < 0.05 ). In the differential expression analysis, there was no intersection between the upregulated genes and the red module genes. However, the intersection of the downregulated genes and the red module genes yielded 4 key genes: dopachrome tautomerase (DCT), keratin 3 (KRT3), keratin 76 (KRT76), and FAM3 metabolic regulation signal molecule B (FAM3B). The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913–1.000). The sensitivity was 0.933, and the specificity was 0.923. The diagnostic model was successfully verified in GSE26549 (AUC = 0.745, CI = 0.638–0.851). Compared with the diagnostic models of the previous studies, the diagnostic efficiency of this model was the highest. The small-molecule drugs, selumetinib and benidipine, were selected according to the gene expression profile and showed binding activity when docking with the above molecules. Conclusions. This study provides new targets and drugs for OLK. These targets could be used as the key diagnostic molecules for long-term follow-up of OLK. The small-molecule drugs selumetinib and benidipine could be used for the prevention and treatment of OSCC.

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Nordon, Galia, Aviram Magen, Ido Guy, and Kira Radinsky. "Learning to Rank Articles for Molecular Queries." Proceedings of the AAAI Conference on Artificial Intelligence 36, no. 11 (June 28, 2022): 12594–600. http://dx.doi.org/10.1609/aaai.v36i11.21532.

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The cost of developing new drugs is estimated at billions of dollars per year. Identification of new molecules for drugs involves scanning existing bio-medical literature for relevant information. As the potential drug molecule is novel, retrieval of relevant information using a simple direct search is less likely to be productive. Identifying relevant papers is therefore a more complex and challenging task, which requires searching for information on molecules with similar characteristics to the novel drug. In this paper, we present the novel task of ranking documents based on novel molecule queries. Given a chemical molecular structure, we wish to rank medical papers that will contribute to a researcher's understanding of the novel molecule drug potential. We present a set of ranking algorithms and molecular embeddings to address the task. An extensive evaluation of the algorithms is performed over the molecular embeddings, studying their performance on a benchmark retrieval corpus, which we share with the community. Additionally, we introduce a heterogeneous edge-labeled graph embedding approach to address the molecule ranking task. Our evaluation shows that the proposed embedding model can significantly improve molecule ranking methods. The system is currently deployed in a targeted drug delivery and personalized medicine research laboratory.

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Namitha K N and V Velmurugan. "Review of bioinformatic tools used in Computer Aided Drug Design (CADD)." World Journal of Advanced Research and Reviews 14, no. 2 (May 30, 2022): 453–65. http://dx.doi.org/10.30574/wjarr.2022.14.2.0394.

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Drug discovery is а time consuming рrосess of finding out a new drug molecule. The process takes many years to complete and needs human resource. These is difficulties have been overcome by introducing computer programmes in drug discovery (CADD) which includes target identification, hit identification, and molecular modification of а lead compound to optimize desired effects and minimize side effects, based on the knowledge of their biological targets. Molecular modelling is the process of designing a molecule with a computer-based collection of programmes (in-silico design) for deriving, representing, and manipulating the structures and reactions of molecules. Numerous Software tools, online data bases and computer programmes are used in the field of CADD in which some relevant, user friendly and precise ones are reviewed in this article. Software is available for personal use and for commercial purposes. All these tools are highly useful in the field of drug design and discovery. The article will be helpful for selecting a tool for computer aided drug design.

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Shakil, Shazi, Adel M. Abuzenadah, Suzan M. Attar, Omar Fathaldin, Rajaa Al-Raddadi, and Mansour I. Sulaiman. "Identification of a putative anti-rheumatoid arthritis molecule by virtual screening." Tropical Journal of Pharmaceutical Research 19, no. 6 (November 13, 2020): 1255–61. http://dx.doi.org/10.4314/tjpr.v19i6.21.

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Purpose: To propose an improved chemical skeleton whose scaffolds could be used for the design of future thymidylate synthase (TS)-inhibitors against rheumatoid arthritis. Methods: The drug discovery platform, ‘MCULE’, was employed for inhibitor-screening. The ‘methotrexate-interaction site’ in the crystal (PDB ID 5X66) was used as a target. One ‘RO5 violation’ was permitted. A maximum of ‘10 rotatable bonds’ and ‘100 diverse molecules’ were also allowed in the protocol. The ‘threshold similarity cut off’ was 0.7. The input values describing the remaining parameters were kept as ‘default’. The ‘Open Babel Linear Fingerprint’ was used for the analyses of molecular descriptors, followed by ADME-check. Results: 4-(4-Methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d]pyrimidine corresponding to the MCULE ID-7590816301-0-93 exhibited the overall best binding with TS. The free energy of binding was -8.6 kcal/mol. A total of 17 amino acid residues were significant for the binding interactions. Importantly, 9 residues were common to methotrexate binding. It satisfied pertinent ADME conditions. Conclusion: 4-(4-Methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d]pyrimidinemay emerge as a potent seed molecule for TS-inhibitor design in the context of rheumatoid arthritis. It has satisfied pertinent ADME features. However, there is need for further wet laboratory validation. Keywords: Anti-rheumatoid arthritis, Inhibitor design, Methotrexate, Seed molecule, Thymidylate synthase, Virtual screening

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Zaki, Magdi E. A., Sami A. Al-Hussain, Vijay H. Masand, Siddhartha Akasapu, Sumit O. Bajaj, Nahed N. E. El-Sayed, Arabinda Ghosh, and Israa Lewaa. "Identification of Anti-SARS-CoV-2 Compounds from Food Using QSAR-Based Virtual Screening, Molecular Docking, and Molecular Dynamics Simulation Analysis." Pharmaceuticals 14, no. 4 (April 13, 2021): 357. http://dx.doi.org/10.3390/ph14040357.

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Due to the genetic similarity between SARS-CoV-2 and SARS-CoV, the present work endeavored to derive a balanced Quantitative Structure−Activity Relationship (QSAR) model, molecular docking, and molecular dynamics (MD) simulation studies to identify novel molecules having inhibitory potential against the main protease (Mpro) of SARS-CoV-2. The QSAR analysis developed on multivariate GA–MLR (Genetic Algorithm–Multilinear Regression) model with acceptable statistical performance (R2 = 0.898, Q2loo = 0.859, etc.). QSAR analysis attributed the good correlation with different types of atoms like non-ring Carbons and Nitrogens, amide Nitrogen, sp2-hybridized Carbons, etc. Thus, the QSAR model has a good balance of qualitative and quantitative requirements (balanced QSAR model) and satisfies the Organisation for Economic Co-operation and Development (OECD) guidelines. After that, a QSAR-based virtual screening of 26,467 food compounds and 360 heterocyclic variants of molecule 1 (benzotriazole–indole hybrid molecule) helped to identify promising hits. Furthermore, the molecular docking and molecular dynamics (MD) simulations of Mpro with molecule 1 recognized the structural motifs with significant stability. Molecular docking and QSAR provided consensus and complementary results. The validated analyses are capable of optimizing a drug/lead candidate for better inhibitory activity against the main protease of SARS-CoV-2.

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Komoto, Yuki, Takahito Ohshiro, and Masateru Taniguchi. "Development of Single-Molecule Electrical Identification Method for Cyclic Adenosine Monophosphate Signaling Pathway." Nanomaterials 11, no. 3 (March 19, 2021): 784. http://dx.doi.org/10.3390/nano11030784.

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Cyclic adenosine monophosphate (cAMP) is an important research target because it activates protein kinases, and its signaling pathway regulates the passage of ions and molecules inside a cell. To detect the chemical reactions related to the cAMP intracellular signaling pathway, cAMP, adenosine triphosphate (ATP), adenosine monophosphate (AMP), and adenosine diphosphate (ADP) should be selectively detected. This study utilized single-molecule quantum measurements of these adenosine family molecules to detect their individual electrical conductance using nanogap devices. As a result, cAMP was electrically detected at the single molecular level, and its signal was successfully discriminated from those of ATP, AMP, and ADP using the developed machine learning method. The discrimination accuracies of a single cAMP signal from AMP, ADP, and ATP were found to be 0.82, 0.70, and 0.72, respectively. These values indicated a 99.9% accuracy when detecting more than ten signals. Based on an analysis of the feature values used for the machine learning analysis, it is suggested that this discrimination was due to the structural difference between the ribose of the phosphate site of cAMP and those of ATP, ADP, and AMP. This method will be of assistance in detecting and understanding the intercellular signaling pathways for small molecular second messengers.

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Spencer, S. C., and J. W. Fabre. "Identification in rat liver and serum of water-soluble class I MHC molecules possibly homologous to the murine Q10 gene product." Journal of Experimental Medicine 165, no. 6 (June 1, 1987): 1595–608. http://dx.doi.org/10.1084/jem.165.6.1595.

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We have identified large quantities of a water-soluble, non-RT1.A class I MHC molecule in the serum of the DA rat strain, with a similar molecule being found in aqueous extracts of DA liver. The non-RT1.A class I molecules have heavy chains of 41 kD, which is smaller than RT1.A class I molecules isolated from liver membranes (45 kD) but larger than water-soluble RT1.A class I molecules previously identified in serum and aqueous extracts of liver and kidney (40 kD). NH3-terminal amino acid sequencing of bulk-purified RT1.A class I molecules and of this novel non-RT1.A class I molecule revealed two substitutions, in the first 25 amino acids, Tyr----His at position 9, and Ala----Ser at position 24. The non-RT1.A class I molecule did not react with any of the well-characterized polymorphic and monomorphic antibodies directed against RT1.Aa class I molecules, but did react with the MRC OX18 antibody. A similar class I molecule could not be identified on liver membranes. The non-RT1.A class I molecule was found in large quantities (approximately 20 micrograms/ml) in the serum of the DA rat strain, and similarly large quantities appeared to be present in the sera of BN, PVG, and LEW.RT1a rats. WAG and LEW.RT1u rats had readily detectable but lower amounts of this molecule in their serum, while LEW and SHR rats had little if any present. This molecule probably represents the rat homologue of the murine Q10 gene product, and is the major class I product in the serum of the DA rat strain.

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Hirota, T., J. W. Lee, P. C. St. John, M. Sawa, K. Iwaisako, T. Noguchi, P. Y. Pongsawakul, et al. "Identification of Small Molecule Activators of Cryptochrome." Science 337, no. 6098 (July 12, 2012): 1094–97. http://dx.doi.org/10.1126/science.1223710.

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Jost, Marco, and Jonathan S. Weissman. "CRISPR Approaches to Small Molecule Target Identification." ACS Chemical Biology 13, no. 2 (January 25, 2018): 366–75. http://dx.doi.org/10.1021/acschembio.7b00965.

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Tomala, Marcin D., Katarzyna Magiera-Mularz, Katarzyna Kubica, Sylwia Krzanik, Bartosz Zieba, Bogdan Musielak, Marcin Pustula, et al. "Identification of small-molecule inhibitors of USP2a." European Journal of Medicinal Chemistry 150 (April 2018): 261–67. http://dx.doi.org/10.1016/j.ejmech.2018.03.009.

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Deng, Xiaodong, Fu Lin, Ya Zhang, Yan Li, Lu Zhou, Bin Lou, Yue Li, et al. "Identification of small molecule sphingomyelin synthase inhibitors." European Journal of Medicinal Chemistry 73 (February 2014): 1–7. http://dx.doi.org/10.1016/j.ejmech.2013.12.002.

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Gade, Anushree Chandrashekhar, Manikanta Murahari, Parasuraman Pavadai, and Maushmi Shailesh Kumar. "Virtual Screening of a Marine Natural Product Database for In Silico Identification of a Potential Acetylcholinesterase Inhibitor." Life 13, no. 6 (May 31, 2023): 1298. http://dx.doi.org/10.3390/life13061298.

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Alzheimer’s disease is characterized by amyloid-beta aggregation and neurofibrillary tangles. Acetylcholinesterase (AChE) hydrolyses acetylcholine and induces amyloid-beta aggregation. Acetylcholinesterase inhibitors (AChEI) inhibit this aggregation by binding to AChE, making it a potential target for the treatment of AD. In this study, we have focused on the identification of potent and safe AChEI from the Comprehensive Marine Natural Product Database (CMNPD) using computational tools. For the screening of CMNPD, a structure-based pharmacophore model was generated using a structure of AChE complexed with the co-crystallized ligand galantamine (PDB ID: 4EY6). The 330 molecules that passed through the pharmacophore filter were retrieved, their drug-likeness was determined, and they were then subjected to molecular docking studies. The top ten molecules were selected depending upon their docking score and were submitted for toxicity profiling. Based on these studies, molecule 64 (CMNPD8714) was found to be the safest and was subjected to molecular dynamics simulations and density functional theory calculations. This molecule showed stable hydrogen bonding and stacked interactions with TYR341, mediated through a water bridge. In silico results can be correlated with in vitro studies for checking its activity and safety in the future.

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Rizvi, Noreen F., John P. Santa Maria, Ali Nahvi, Joel Klappenbach, Daniel J. Klein, Patrick J. Curran, Matthew P. Richards, et al. "Targeting RNA with Small Molecules: Identification of Selective, RNA-Binding Small Molecules Occupying Drug-Like Chemical Space." SLAS DISCOVERY: Advancing the Science of Drug Discovery 25, no. 4 (November 8, 2019): 384–96. http://dx.doi.org/10.1177/2472555219885373.

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Although the potential value of RNA as a target for new small molecule therapeutics is becoming increasingly credible, the physicochemical properties required for small molecules to selectively bind to RNA remain relatively unexplored. To investigate the druggability of RNAs with small molecules, we have employed affinity mass spectrometry, using the Automated Ligand Identification System (ALIS), to screen 42 RNAs from a variety of RNA classes, each against an array of chemically diverse drug-like small molecules (~50,000 compounds) and functionally annotated tool compounds (~5100 compounds). The set of RNA–small molecule interactions that was generated was compared with that for protein–small molecule interactions, and naïve Bayesian models were constructed to determine the types of specific chemical properties that bias small molecules toward binding to RNA. This set of RNA-selective chemical features was then used to build an RNA-focused set of ~3800 small molecules that demonstrated increased propensity toward binding the RNA target set. In addition, the data provide an overview of the specific physicochemical properties that help to enable binding to potential RNA targets. This work has increased the understanding of the chemical properties that are involved in small molecule binding to RNA, and the methodology used here is generally applicable to RNA-focused drug discovery efforts.

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Demir, Firuz, and George Kirczenow. "Communication: Identification of the molecule–metal bonding geometries of molecular nanowires." Journal of Chemical Physics 134, no. 12 (March 28, 2011): 121103. http://dx.doi.org/10.1063/1.3571473.

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Erdogan, Evrim, and Michael Kalafatis. "Identification of Sulfo-Tyrosines of Factor V." Blood 104, no. 11 (November 16, 2004): 1731. http://dx.doi.org/10.1182/blood.v104.11.1731.1731.

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Abstract The factor Va molecule is the essential cofactor of the prothrombinase complex. This complex composed of factor Xa and factor Va assembled on a platelet membrane-surface in the presence of Ca2+ ions converts membrane-bound prothrombin to thrombin. Single chain factor V does not bind factor Xa. Single-chain factor V is cleaved by thrombin first at Arg709 followed by cleavages at Arg1018 and Arg1545 to produce the heavy and light chains of the active cofactor (factor Va) and two activation peptides. Efficient thrombin cleavage and activation of factor V is essential for cofactor function and requires tyrosine sulfation. Tyrosine sulfation of factor V also appears to regulate its activity. Seven tyrosine residues in factor V, Tyr665, Tyr696, Tyr698, Tyr1494, Tyr1510, Tyr1515, and Tyr1565 have been identified as potential sites of sulfation. However, which residues are sulfated and their contribution to procofactor activation and cofactor function still remain to be elucidated. Two of the sulfation sites Tyr696 and Tyr698 are located in the acidic amino acid region near to the first required thrombin cleavage site at Arg709. Recent data demonstrated that these residues are essential for factor V activation and cofactor activity. Another acidic amino acid region, 1490–1520 is adjacent to the thrombin cleavage site at Arg1545 required for light chain formation. This region also contains three potential sulfation sites at residues 1494, 1510, and 1515 and was shown to be required for optimum procofactor activation. To ascertain which of these three residues is important for procofactor activation, site-directed mutagenesis was used to create recombinant factor V molecules with mutations 1493DY1494→AF, 1508DDY1510→AAF and 1514DY1515→AF. The clotting and cofactor activity of the 1493DY1494→AF and 1514DY1515→AF mutants was similar to the clotting activity observed with the wild type recombinant factor Va molecule following activation by thrombin or RVV-V activator. In contrast, under similar experimental conditions recombinant factor V with the substitution 1508DDY1510→AAF was deficient in its clotting activity and had impaired cofactor activity. Moreover, following prolonged incubation with thrombin, no light chain formation was observed in the factor V molecule bearing the 1508DDY1510→AAF mutation. Thus, amino acid residues 1508–1510 of factor V are required for thrombin interaction with the procofactor which in turn appears necessary for cleavage at Arg1545. Studies of sulfated proteins have shown that the effect of sulfo-tyrosines on protein structure/function can be preserved by replacing them with glutamic acid. To explicitly identify the sulfated tyrosines on the factor V molecule, we mutated Tyr696, Tyr698 and Tyr1510 to glutamic acid and transfected them into COS-7L cells. Expression was performed in the presence of media containing or devoid of sulfate. In the presence of sulfate, the cofactor and clotting activities of the DY696DY698→DEDE and DDY1510→DDE mutants, separately were similar to the wild type recombinant factor Va molecule. However, in the absence of sulfate, the wild type and the mutant recombinant factor V molecules had both impaired cofactor activity and clotting activity following their activation with thrombin. However, their respective activity was higher than the activity of the factor V molecule bearing the 1508DDY1510→AAF mutation. Our data suggest that residues 696, 698, and 1510 of factor V appear to be sulfated and might be important for procofactor activation and cofactor function.

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Brouard, Céline, Antoine Bassé, Florence d’Alché-Buc, and Juho Rousu. "Improved Small Molecule Identification through Learning Combinations of Kernel Regression Models." Metabolites 9, no. 8 (August 1, 2019): 160. http://dx.doi.org/10.3390/metabo9080160.

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In small molecule identification from tandem mass (MS/MS) spectra, input–output kernel regression (IOKR) currently provides the state-of-the-art combination of fast training and prediction and high identification rates. The IOKR approach can be simply understood as predicting a fingerprint vector from the MS/MS spectrum of the unknown molecule, and solving a pre-image problem to find the molecule with the most similar fingerprint. In this paper, we bring forward the following improvements to the IOKR framework: firstly, we formulate the IOKRreverse model that can be understood as mapping molecular structures into the MS/MS feature space and solving a pre-image problem to find the molecule whose predicted spectrum is the closest to the input MS/MS spectrum. Secondly, we introduce an approach to combine several IOKR and IOKRreverse models computed from different input and output kernels, called IOKRfusion. The method is based on minimizing structured Hinge loss of the combined model using a mini-batch stochastic subgradient optimization. Our experiments show a consistent improvement of top-k accuracy both in positive and negative ionization mode data.

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Lopez-Bernad, F., E. Del Cacho, M. Gallego, J. Quilez, and C. Sanchez-Acedo. "Identification of a fibronectin-like molecule on Eimeria tenella." Parasitology 113, no. 6 (December 1996): 505–10. http://dx.doi.org/10.1017/s0031182000067548.

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SUMMARYThe attachment of Eimeria tenella to its target cells as an obligatory intracellular pathogen is essential for the development of disease. Previous reports have established that other intracellular protozoa parasites have either fibronectin, an adhesion protein, or fibronectin receptors, both of which are involved in the interaction with the host cells. In this current research, studies have been undertaken to visualize a surface component that may be involved in the attachment of E. tenella to host cells. For this purpose, monoclonal antibodies, both anti-chicken and anti-human fibronectin, and also anti-chicken integrin were used. Our results show a fibronectin-like molecule with an apparent molecular weight of 110 kDa in mature schizonts and microgametes. Staining with serum directed against chicken integrin revealed immunoreactivity within mature schizonts. Both the fibronectin-like molecule and the integrin may play an important role in the parasite stage-cell interaction and the promotion of parasite uptake.

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Gubin, Alexander N., J. Muthoni Njoroge, Urszula Wojda, Svetlana D. Pack, Maria Rios, Marion E. Reid, and Jeffery L. Miller. "Identification of the Dombrock blood group glycoprotein as a polymorphic member of the ADP-ribosyltransferase gene family." Blood 96, no. 7 (October 1, 2000): 2621–27. http://dx.doi.org/10.1182/blood.v96.7.2621.

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Abstract Identification of the 25 known human blood group molecules is of fundamental importance for the fields of erythroid cell biology and transfusion medicine. Here we provide the first molecular description of the “Dombrock” blood group system. A candidate gene was identified by in silico analyses of approximately 5000 expressed sequence tags (ESTs) from terminally differentiating human erythroid cells. Transfection experiments demonstrated specific binding of anti-Dombrock and confirmed glycosylphosphatidylinositol membrane attachment. Dombrock expression is developmentally regulated during erythroid differentiation and occurs at highest levels in the fetal liver. Homology studies suggest that the Dombrock molecule is a member of the adenosine 5′-diphosphate (ADP)–ribosyltransferase ectoenzyme gene family. Genotypic comparisons suggest Doa versus Dob antigenicity results from a single amino acid substitution within an encoded arginine-glycine-aspartic acid (RGD) motif of the molecule.

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Gubin, Alexander N., J. Muthoni Njoroge, Urszula Wojda, Svetlana D. Pack, Maria Rios, Marion E. Reid, and Jeffery L. Miller. "Identification of the Dombrock blood group glycoprotein as a polymorphic member of the ADP-ribosyltransferase gene family." Blood 96, no. 7 (October 1, 2000): 2621–27. http://dx.doi.org/10.1182/blood.v96.7.2621.h8002621_2621_2627.

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Identification of the 25 known human blood group molecules is of fundamental importance for the fields of erythroid cell biology and transfusion medicine. Here we provide the first molecular description of the “Dombrock” blood group system. A candidate gene was identified by in silico analyses of approximately 5000 expressed sequence tags (ESTs) from terminally differentiating human erythroid cells. Transfection experiments demonstrated specific binding of anti-Dombrock and confirmed glycosylphosphatidylinositol membrane attachment. Dombrock expression is developmentally regulated during erythroid differentiation and occurs at highest levels in the fetal liver. Homology studies suggest that the Dombrock molecule is a member of the adenosine 5′-diphosphate (ADP)–ribosyltransferase ectoenzyme gene family. Genotypic comparisons suggest Doa versus Dob antigenicity results from a single amino acid substitution within an encoded arginine-glycine-aspartic acid (RGD) motif of the molecule.

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Kulyk, Ya S. "EPITOPES IDENTIFICATION OF BROADLY NEUTRALIZING MONOCLONAL ANTIBODIES AGAINST Corynebacterium diphtheriae EXOTOXIN." Biotechnologia Acta 15, no. 4 (August 31, 2022): 37–40. http://dx.doi.org/10.15407/biotech15.04.037.

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Background. Better and high-potency vaccines against diphtheria are urgently needed to provide broader protection against diverse strains and subtypes. Identification of novel broadly neutralizing epitopes targeted by protective antibodies could aid in such efforts. Aim. In this study we focused on the search of binding sites identification of anti diphtheria toxin monoclonal antibodies and their neutralizing activity to block binding of recombinant exotoxin derivates with host receptors. Methods. Vero cells were cultured in the complete RPMI-1640 medium under standard conditions and used for flow cytometry assay. Recombinant antigens and products of tryptic hydrolysis of CRM197 and SbB were characterized by Ni2+-NTA affinity chromatography and SDS-PAGE under reducing conditions with following ECL Western-Blot using several hybridomas clones of anti-diphtheria toxin monoclonal antibodies. Results. ECL western blot film results for clone 9.1-E11 showed the specific binding both to whole CRM197 molecule, and to almost all fragments of CRM197 formed as a result of limited proteolysis. In particular, a band corresponding to SbB in molecular weight can be identified. Thus, epitope region of the CRM197 molecule specific to 9.1-E1 mAbs is located within the structure of SbB. At the same time 16.4-E9 clone antibodies had high specificity to R-domain of SbB. In addition, both hybridoma clones antibodies have neutralizing activity against the DT binding subunit, which is a key factor in blocking between cell receptor and it ligand, C.diphtheriae exotoxin. Conclusions. The results obtained indicate that obtained antibodies are prospective for improving new diagnostic tools and therapeutic agents, which are used for treatment and understanding of the molecular mechanisms of diphtheria pathogenesis.

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Wierzba, Konstanty, Makoto Muroi, and Hiroyuki Osada. "Proteomics accelerating the identification of the target molecule of bioactive small molecules." Current Opinion in Chemical Biology 15, no. 1 (February 2011): 57–65. http://dx.doi.org/10.1016/j.cbpa.2010.10.009.

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Bukhari, Syed Nasir Abbas, Mervat Abdelaziz Elsherif, Kashaf Junaid, Hasan Ejaz, Pravej Alam, Abdul Samad, Rahul D. Jawarkar, and Vijay H. Masand. "Perceiving the Concealed and Unreported Pharmacophoric Features of the 5-Hydroxytryptamine Receptor Using Balanced QSAR Analysis." Pharmaceuticals 15, no. 7 (July 5, 2022): 834. http://dx.doi.org/10.3390/ph15070834.

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The 5-hydroxytryptamine receptor 6 (5-HT6) has gained attention as a target for developing therapeutics for Alzheimer’s disease, schizophrenia, cognitive dysfunctions, anxiety, and depression, to list a few. In the present analysis, a larger and diverse dataset of 1278 molecules covering a broad chemical and activity space was used to identify visual and concealed structural features associated with binding affinity for 5-HT6. For this, quantitative structure–activity relationships (QSAR) and molecular docking analyses were executed. This led to the development of a statistically robust QSAR model with a balance of excellent predictivity (R2tr = 0.78, R2ex = 0.77), the identification of unreported aspects of known features, and also novel mechanistic interpretations. Molecular docking and QSAR provided similar as well as complementary results. The present analysis indicates that the partial charges on ring carbons present within four bonds from a sulfur atom, the occurrence of sp3-hybridized carbon atoms bonded with donor atoms, and a conditional occurrence of lipophilic atoms/groups from nitrogen atoms, which are prominent but unreported pharmacophores that should be considered while optimizing a molecule for 5-HT6. Thus, the present analysis led to identification of some novel unreported structural features that govern the binding affinity of a molecule. The results could be beneficial in optimizing the molecules for 5-HT6.

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Gonzales, Amanda M., and Robert A. Orlando. "A Sensitive Aβ Oligomerization Assay for Identification of Small Molecule Inhibitors." Open Biotechnology Journal 3, no. 1 (November 12, 2009): 108–16. http://dx.doi.org/10.2174/1874070700903010108.

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Amyloid deposits found in Alzheimer’s disease result from aggregation of Aβ peptide which leads to loss of synaptic function, chronic microglial activation and cognitive impairment. Because of this, identification of small molecule inhibitors of Aβ aggregation as potential therapeutics is a topic of current interest. The majority of inhibitor screening approaches rely on in vitro assays that lack the necessary sensitivity to distinguish low-molecular weight Aβ oligomers from larger, more advanced-stage fibrillar structures. Differentiating between these two structures is of vital concern since recent studies indicate that small, early-stage Aβ oligomers are the most neurotoxic form of peptide aggregate. To address this limitation, we have explored the adaptability of a recently described ELISA-based assay for discovery of small molecule inhibitors of Aβ oligomerization. Results show that this assay is highly sensitive as it is able to quantify Aβ oligomers with as little as 80 nM input peptide. In addition, data were obtained re-confirming the function of curcumin as a potent inhibitor of Aβ aggregation (IC50 = 2 μM) and defining its inhibitor:peptide functional stoichiometry. Further examination of other known anti-aggregation compounds showed that this assay is able to discriminate between inhibitors of early-stage, low-molecular weight oligomers and later-stage, high-molecular weight fibrillar structures. These findings indicate that this new ELISA-based assay is capable of identifying novel small molecule inhibitors that function during the initial stages of Aβ peptide assembly.

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Joost, Maximilian, Matthew Nava, Wesley J. Transue, Marie-Aline Martin-Drumel, Michael C. McCarthy, David Patterson, and Christopher C. Cummins. "Sulfur monoxide thermal release from an anthracene-based precursor, spectroscopic identification, and transfer reactivity." Proceedings of the National Academy of Sciences 115, no. 23 (May 17, 2018): 5866–71. http://dx.doi.org/10.1073/pnas.1804035115.

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Sulfur monoxide (SO) is a highly reactive molecule and thus, eludes bulk isolation. We report here on synthesis and reactivity of a molecular precursor for SO generation, namely 7-sulfinylamino-7-azadibenzonorbornadiene (1). This compound has been shown to fragment readily driven by dinitrogen expulsion and anthracene formation on heating in the solid state and in solution, releasing SO at mild temperatures (<100 °C). The generated SO was detected in the gas phase by MS and rotational spectroscopy. In solution, 1 allows for SO transfer to organic molecules as well as transition metal complexes.

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Li, Chang Cheng, Lai Wu Yin, Dong Chen, and Shu Jie Xu. "Lossless Compression of Weak Electrical Signal of Ginseng Molecule Based on Discrete Wavelet Transform and Siesta Program." Advanced Materials Research 986-987 (July 2014): 1950–53. http://dx.doi.org/10.4028/www.scientific.net/amr.986-987.1950.

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This paper proposed the electron density of time series by using the Siesta software to calculate the weak electrical signals of ginseng molecule, combining with the lifting scheme DWT to remove ginseng molecular spatial redundancy. For the acquisition and identification of weak electrical signals of ginseng molecule in physical environment , based on the analysis of collection and identification’s principles, the noise coefficient is removed to reconstruct the signal and retain the useful signal components through applying the multi-decomposition of DWT transform to divide weak electrical signals of ginseng molecule into wavelet coefficients of different scales. The experimental results show that the multi-resolution analysis of DWT transform is performed for the weak electrical signal of ginseng molecule with different rhythms and different frequency ranges, and the weak electrical signal size of ginseng molecule before and after compression, the percentage of high frequency coefficients set to zero, and the average energy percentage after compression are, respectively, increased to 77.73%, 46.88%, and 99.99%. This algorithm operates fast enough to ease hardware implementation, providing an effective method for lossless compression of the weak electrical signals of ginseng molecule.

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Tazi, Mehdi, Thierry Roisnel, Florence Mongin, and William Erb. "Ferrocenecarboxylic anhydride: identification of a new polymorph." Acta Crystallographica Section C Structural Chemistry 73, no. 10 (September 20, 2017): 760–66. http://dx.doi.org/10.1107/s205322961701124x.

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A new monoclinic polymorph of ferrocenecarboxylic anhydride, [Fe2(C5H5)2(C12H8O3)], was obtained. Three molecules are present in the asymmetric unit, two of them being nearly identical (r.m.s. deviation = 0.11 Å), with the Fe atoms on the same side of the anhydride functional group. In the third molecule, the two Fe atoms are located at opposite sides of the functional group (ferrocene–ferrocene pseudo-torsion angle = 146.2°), a very unsual feature in metallocene anhydrides. A network of weak intermolecular hydrogen bonds was also disclosed.

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Shibayama, Hirohiko, Emi Takai, Itaru Matsumura, Michiyoshi Kouno, Eiichi Morii, Yukihiko Kitamura, Junji Takeda, and Yuzuru Kanakura. "Identification of a Cytokine-induced Antiapoptotic Molecule Anamorsin Essential for Definitive Hematopoiesis." Journal of Experimental Medicine 199, no. 4 (February 16, 2004): 581–92. http://dx.doi.org/10.1084/jem.20031858.

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Many growth factors and cytokines prevent apoptosis. Using an expression cloning method, we identified a novel antiapoptotic molecule named Anamorsin, which does not show any homology to known apoptosis regulatory molecules such as Bcl-2 family, caspase family, or signal transduction molecules. The expression of Anamorsin was completely dependent on stimulation with growth factors such as interleukin 3, stem cell factor, and thrombopoietin in factor-dependent hematopoietic cell lines, and forced expression of Anamorsin conferred resistance to apoptosis caused by growth factor deprivation in vitro. Furthermore, Anamorsin was found to act as an antiapoptotic molecule in vivo because Anamorsin−/− mice die in late gestation due to defective definitive hematopoiesis in the fetal liver (FL). Although the number of hematopoietic stem/progenitor cells in the FL did not decrease in these mice, myeloid, and particularly erythroid colony formation in response to cytokines, was severely disrupted. Also, Anamorsin−/− erythroid cells initiated apoptosis during terminal maturation. As for the mechanism of Anamorsin-mediated cell survival, a microarray analysis revealed that the expression of Bcl-xL and Jak2 was severely impaired in the FL of Anamorsin−/− mice. Thus, Anamorsin is considered to be a necessary molecule for hematopoiesis that mediates antiapoptotic effects of various cytokines.

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DeSouza, Nicole R., Danielle Quaranto, Michelle Carnazza, Tara Jarboe, Raj K. Tiwari, and Jan Geliebter. "Interactome of Long Non-Coding RNAs: Transcriptomic Expression Patterns and Shaping Cancer Cell Phenotypes." International Journal of Molecular Sciences 24, no. 12 (June 8, 2023): 9914. http://dx.doi.org/10.3390/ijms24129914.

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RNA biology has gained extensive recognition in the last two decades due to the identification of novel transcriptomic elements and molecular functions. Cancer arises, in part, due to the accumulation of mutations that greatly contribute to genomic instability. However, the identification of differential gene expression patterns of wild-type loci has exceeded the boundaries of mutational study and has significantly contributed to the identification of molecular mechanisms that drive carcinogenic transformation. Non-coding RNA molecules have provided a novel avenue of exploration, providing additional routes for evaluating genomic and epigenomic regulation. Of particular focus, long non-coding RNA molecule expression has been demonstrated to govern and direct cellular activity, thus evidencing a correlation between aberrant long non-coding RNA expression and the pathological transformation of cells. lncRNA classification, structure, function, and therapeutic utilization have expanded cancer studies and molecular targeting, and understanding the lncRNA interactome aids in defining the unique transcriptomic signatures of cancer cell phenotypes.

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Botelho, Fernanda D., Marcelo C. dos Santos, Arlan da S. Gonçalves, Kamil Kuca, Martin Valis, Steven R. LaPlante, Tanos C. C. França, and Joyce S. F. D. de Almeida. "Ligand-Based Virtual Screening, Molecular Docking, Molecular Dynamics, and MM-PBSA Calculations towards the Identification of Potential Novel Ricin Inhibitors." Toxins 12, no. 12 (November 26, 2020): 746. http://dx.doi.org/10.3390/toxins12120746.

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Ricin is a toxin found in the castor seeds and listed as a chemical weapon by the Chemical Weapons Convention (CWC) due to its high toxicity combined with the easiness of obtention and lack of available antidotes. The relatively frequent episodes of usage or attempting to use ricin in terrorist attacks reinforce the urge to develop an antidote for this toxin. In this sense, we selected in this work the current RTA (ricin catalytic subunit) inhibitor with the best experimental performance, as a reference molecule for virtual screening in the PubChem database. The selected molecules were then evaluated through docking studies, followed by drug-likeness investigation, molecular dynamics simulations and Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) calculations. In every step, the selection of molecules was mainly based on their ability to occupy both the active and secondary sites of RTA, which are located right next to each other, but are not simultaneously occupied by the current RTA inhibitors. Results show that the three PubChem compounds 18309602, 18498053, and 136023163 presented better overall results than the reference molecule itself, showing up as new hits for the RTA inhibition, and encouraging further experimental evaluation.

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GRAHAM, P., K. W. D. LEDINGHAM, R. P. SINGHAL, S. M. HANKIN, T. MCCANNY, X. FANG, P. F. TADAY, A. J. LANGLEY, and C. KOSMIDIS. "Angular distributions of fragment ions arising from tetrahedral CH3I and isomer identification using intense laser fields." Laser and Particle Beams 19, no. 2 (April 2001): 187–93. http://dx.doi.org/10.1017/s0263034601192037.

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Utilizing an ultraintense (1016 W cm−2) fs laser, the laser/matter interaction of the tetrahedral CH3I molecule is investigated. A mass spectrum and the angular distributions of fragment ions arising from Coulomb explosion of molecular ions, obtained with linearly polarized light, are presented. The distributions for In+ (n ≤ 7), CHm+ (m ≤ 3), Cp+ (p ≤ 4) and H+ ions are all anisotropic and maximal when the polarization lies along the spectrometer axis. The molecule hence seems to behave as a diatomic, with the fragment ions being ejected along the field direction. Also presented are mass spectra of the isomers 1- and 2-nitropropane, which are explosive species, taken for horizontal and vertical polarizations at both 375 and 750 nm. It is shown that femtosecond laser mass spectrometry (FLMS) can be used to distinguish between these two isomers through their differing dissociation patterns. Isomer identification is important for many different applications and FLMS may provide a means of achieving this for a wide range of molecules.

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Huang, Zhongkai, Xiangyang Peng, Cheng Peng, Jin Huang, Maolin Bo, Chuang Yao, and Jibiao Li. "Detecting Air Pollutant Molecules Using Tube-Shaped Single Electron Transistor." Molecules 26, no. 23 (November 24, 2021): 7098. http://dx.doi.org/10.3390/molecules26237098.

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An air pollution detector is proposed based on a tube-shaped single-electron transistor (SET) sensor. By monitoring the flow control component of the detector, each air pollutant molecule can be placed at the center of a SET nanopore and is treated as an island of the SET device in the same framework. Electron transport in the SET was incoherent, and the performances of the SET were sensitive at the single molecule level. Employing first-principles calculations, electronic features of an air pollutant molecule within a tube-shaped SET environment were found to be independent of the molecule rotational orientations with respect to axis of symmetry, unlike the electronic features in a conventional SET environment. Charge stability diagrams of the island molecules were demonstrated to be distinct for each molecule, and thus they can serve as electronic fingerprints for detection. Using the same setup, quantification of the air pollutant can be realized at room temperature as well. The results presented herein may help provide guidance for the identification and quantification of various types of air pollutants at the molecular level by treating the molecule as the island of the SET component in the proposed detector.

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Sunkara, Muni Sireesha, Vinutha Kuchana, Jyothi Vemuri, and Dipankar Bhowmik. "Ensemble Pharmacophore Meets Molecular Docking: A Novel Screening Approach for the Identification of B-Raf Kinase Inhibitors." Trends in Sciences 20, no. 1 (November 26, 2022): 6403. http://dx.doi.org/10.48048/tis.2023.6403.

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In US about 106110 diagnosed as melanomas, 7,180 people expected to die due to melanoma. B-RAF is a cytoplasmic serine - threonine kinase that is found in a mutated form in melanoma and colorectal cancer. Sorafenib was initially introduced as a B-RAF inhibitor in melanoma. Hence it is taken as a pivot molecule in our study. Four potent B-Raf kinase inhibitors (Sorafenib, Regorafenib, N-desmethyl sorafenib & Donafenib) are used to build a pharmacophore model with ‘PharmaGist webserver’ which generated a 5-point hypothesis. The best model with score of 27.780, was used to screen the Zinc database of ZINCPharmer web server to obtain similar pharmacophore hits. By applying filters like Lipinski rule, RMSD criteria in ZINCPharmer top ten hits were identified. Subsequently, molecular docking was performed on wild (1UWH) and mutated (3IDP) B-Raf kinase protein targets by using GLIDE 5.6 (Schrödinger), to prioritize top lead molecules. Further these molecules are subjected to ADME Properties Prediction by Qik Prop module. Among ten, nine molecules have glide scores in the range nearer to the standard molecule i.e., Sorafenib. Finally, we conclude that ZINC02853810 may act as a powerful inhibitor against both wild and mutant type B-Raf kinase as it has highest glide scores than the Standard. GRAPHICAL ABSTRACT

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Kindt, G. C., J. G. van de Winkel, S. A. Moore, and C. L. Anderson. "Identification and structural characterization of Fc gamma-receptors on pulmonary alveolar macrophages." American Journal of Physiology-Lung Cellular and Molecular Physiology 260, no. 6 (June 1, 1991): L403—L411. http://dx.doi.org/10.1152/ajplung.1991.260.6.l403.

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Little is known about the structure of the cell surface receptors for the Fc portion of immunoglobulin G (Fc gamma R) on tissue macrophages. Studies on leukocytes indicate the existence of three classes of Fc gamma R, denoted I, II, and III. The purpose of this study was to structurally characterize Fc gamma R on alveolar macrophages obtained by bronchoalveolar lavage, comparing them with Fc gamma R of monocytes, neutrophils, and U937 cells. Flow-cytometric evaluation, utilizing anti-Fc gamma R class-specific monoclonal antibodies, showed that alveolar macrophages expressed three Fc gamma R classes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the immunopurified Fc gamma R molecules revealed the following apparent molecular mass for each Fc gamma R class: Fc gamma RI, 70 kDa; Fc gamma RII, 44 kDa; and Fc gamma RIII, 57-65 kDa. RNA blot analysis demonstrated a 1.7-kb transcript for Fc gamma RI, 2.5 and 1.6 kb transcripts for Fc gamma RII, and a 2.2 kb mRNA for Fc gamma RIII. Fc gamma RII displayed the high-responder/low-responder polymorphism. Fc gamma RIII did not express the neutrophil antigen-type specific structural polymorphism of the deglycosylated Fc gamma R molecule and appeared to be a transmembrane molecule.

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Alomari, Arqam, Robert Gowland, Callum Southwood, Jak Barrow, Zoe Bentley, Jashel Calvin-Nelson, Alice Kaminski, et al. "Identification of Novel Inhibitors of Escherichia coli DNA Ligase (LigA)." Molecules 26, no. 9 (April 25, 2021): 2508. http://dx.doi.org/10.3390/molecules26092508.

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Present in all organisms, DNA ligases catalyse the formation of a phosphodiester bond between a 3′ hydroxyl and a 5′ phosphate, a reaction that is essential for maintaining genome integrity during replication and repair. Eubacterial DNA ligases use NAD+ as a cofactor and possess low sequence and structural homology relative to eukaryotic DNA ligases which use ATP as a cofactor. These key differences enable specific targeting of bacterial DNA ligases as an antibacterial strategy. In this study, four small molecule accessible sites within functionally important regions of Escherichia coli ligase (EC-LigA) were identified using in silico methods. Molecular docking was then used to screen for small molecules predicted to bind to these sites. Eight candidate inhibitors were then screened for inhibitory activity in an in vitro ligase assay. Five of these (geneticin, chlorhexidine, glutathione (reduced), imidazolidinyl urea and 2-(aminomethyl)imidazole) showed dose-dependent inhibition of EC-LigA with half maximal inhibitory concentrations (IC50) in the micromolar to millimolar range (11–2600 µM). Two (geneticin and chlorhexidine) were predicted to bind to a region of EC-LigA that has not been directly investigated previously, raising the possibility that there may be amino acids within this region that are important for EC-LigA activity or that the function of essential residues proximal to this region are impacted by inhibitor interactions with this region. We anticipate that the identified small molecule binding sites and inhibitors could be pursued as part of an antibacterial strategy targeting bacterial DNA ligases.

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Zhang, Baixia, Shuaibing He, Chenyang Lv, Yanling Zhang, and Yun Wang. "GEPSI: A Gene Expression Profile Similarity-Based Identification Method of Bioactive Components in Traditional Chinese Medicine Formula." Evidence-Based Complementary and Alternative Medicine 2018 (2018): 1–9. http://dx.doi.org/10.1155/2018/6935350.

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The identification of bioactive components in traditional Chinese medicine (TCM) is an important part of the TCM material foundation research. Recently, molecular docking technology has been extensively used for the identification of TCM bioactive components. However, target proteins that are used in molecular docking may not be the actual TCM target. For this reason, the bioactive components would likely be omitted or incorrect. To address this problem, this study proposed the GEPSI method that identified the target proteins of TCM based on the similarity of gene expression profiles. The similarity of the gene expression profiles affected by TCM and small molecular drugs was calculated. The pharmacological action of TCM may be similar to that of small molecule drugs that have a high similarity score. Indeed, the target proteins of the small molecule drugs could be considered TCM targets. Thus, we identified the bioactive components of a TCM by molecular docking and verified the reliability of this method by a literature investigation. Using the target proteins that TCM actually affected as targets, the identification of the bioactive components was more accurate. This study provides a fast and effective method for the identification of TCM bioactive components.

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KARABOĞA, Seda, and Gürcan YILDIRIM. "A comparative investigation for identification of N-(4-dimethylamino 3,5-dinitrophenyl)maleimide." Journal of New Results in Science 12, no. 1 (April 30, 2023): 27–46. http://dx.doi.org/10.54187/jnrs.1241130.

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This study has identified the characteristic behaviors of N-(4-dimethylamino 3,5-dinitrophenyl)maleimide molecule using ab initio Hartree-Fock (HF) and density functional theory (DFT) based on Becke’s three-parameter hybrid exchange functional combined with Lee-Yang-Parr non-local correlation function (HF/B3LYP and DFT/B3LYP) at 6-311G++(d,p) level of theory for the first time. On this basis, the optimized molecular structures, some thermodynamic features at 300 K, function groups of structures, charge distributions-dipole moments, molecular charge transfer regions, spectroscopic characteristic properties, vibrational frequencies, nuclear magnetic resonance chemical shifts of 13C-NMR and 1H-NMR spectra, and corresponding vibrational assignments have been investigated in detail. Comparisons between some experimental findings and theoretical results are performed to test the reliability of the calculation method preferred in the study. The comparison results in high correlation parameters such as R2 =0.976 and R2 =0.985 for the molecular structures and vibrational frequencies in the DFT and HF calculation levels, respectively. Moreover, the obtained vibrational frequencies and calculated results are in good agreement with the experimental data. Additionally, the simulations of highest/lowest occupied/unoccupied molecular orbital (HOMO and LUMO), molecular electrostatic potential (MEP), and electrostatic potential (ESP) maps have shown that there appear strong non-uniform intra-molecular charge distributions (ICT), electron engagements, lone pairs of electrons, π-π* conjugative effects based on the bond weakening, and intermolecular hydrogen bonding in the compound. Correspondingly, the molecule with the electrophilic reactive and nucleophilic regions has been noted to exhibit kinetical chemical stability. All the discussions have been confirmed by means of the findings of optimized molecular structures and vibrational frequencies belonging to the molecule.

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Lawes, Patrick, Mauro Boero, Rabei Barhoumi, Svetlana Klyatskaya, Mario Ruben, and Jean-Pierre Bucher. "Hierarchical Self-Assembly and Conformation of Tb Double-Decker Molecular Magnets: Experiment and Molecular Dynamics." Nanomaterials 13, no. 15 (August 1, 2023): 2232. http://dx.doi.org/10.3390/nano13152232.

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Nanostructures, fabricated by locating molecular building blocks in well-defined positions, for example, on a lattice, are ideal platforms for studying atomic-scale quantum effects. In this context, STM data obtained from self-assembled Bis(phthalocyaninato) Terbium (III) (TbPc2) single-molecule magnets on various substrates have raised questions about the conformation of the TbPc2 molecules within the lattice. In order to address this issue, molecular dynamics simulations were carried out on a 2D assembly of TbPc2 molecules. The calculations are in excellent agreement with the experiment, and thus improve our understanding of the self-assembly process. In particular, the calculated electron density of the molecular assembly compares well with STM contrast of self-assembled TbPc2 on Au(111), simultaneously providing the conformation of the two Pc ligands of the individual double-decker molecule. This approach proves valuable in the identification of the STM contrast of LnPc2 layers and could be used in similar cases where it is difficult to interpret the STM images of an assembly of molecular complexes.

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Bradner, James, Yong-Son Kim, Angela Koehler, Masaoki Kawasumi, Xiaodong Li, Stuart L. Schreiber, and Paul Nghiem. "Identification and Characterization of Novel Small-Molecule Inhibitors of the Replication Checkpoint." Blood 104, no. 11 (November 16, 2004): 763. http://dx.doi.org/10.1182/blood.v104.11.763.763.

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Abstract Background The replication (G2/M) checkpoint is principally mediated by the serine/threonine protein kinase ATR (ataxia telangiectasia mutated and Rad3-related). ATR is a large (350 kD) member of the phosphatidylinositol kinase related kinase family. After exposure to genotoxic or replication stress, ATR halts cell cycle progression, allowing DNA repair complexes time enough to restore the fidelity of the genome prior to cell division. Previous experiments have demonstrated that cancer cells with p53 mutation are critically dependent on ATR-mediated arrest of the cell cycle. Industrial approaches to identify ATR inhibitors have failed likely as a result of protein insolubility. Methods We have undertaken a novel chemical genetic approach employing small molecule microarrays (SMMs) to identify molecules with high binding specificity for ATR. Three diversity-oriented combinatorial chemical libraries of more than 15,000 entities were generated by split-pool synthesis in solid phase on polystyrene macrobead supports. Compounds were robotically printed in microarray format on glass slides. Four analogs of FK506 were printed as positive controls. Extracts were prepared from mammalian cells transfected with over-expression constructs of FLAG-tagged ATR, FKBP12 and GFP. A protocol was developed and optimized for screening employing a primary anti-FLAG mouse monoclonal antibody and Cy5-fluorophore labeled anti-mouse antibody. Data analysis for small molecule binders was performed with GenePix software on an Axon Scanner. Biological activity of these molecules was analyzed in the context of mitotic spread and chromosomal fragility assays. Results Protein expression and antibody fidelity was verified by Western blot. The lysate-based SMM screening approach was optimized and validated by recognition of an interaction between over-expressed, epitope-tagged FKBP12 and analogs of FK506. Six small molecule hits suggesting ATR binding were identified and verified by triplicate microarray assays. Positive compounds were structurally similar members of a dihydropyrancarboxamide library suggesting recognition of a common target. Mitotic spread analysis of cells treated with two of these molecules and hydroxyurea demonstrated the premature chromatin condensation phenotype characteristic of replication checkpoint inhibition. Chromosomal fragility was notably augmented by these molecules as well. Chemosensitivity following replication stress was witnessed in p53-negative cells relative to an otherwise identical wild-type cell line. Conclusions Classical approaches to drug discovery are often limited by challenges in protein biochemistry such as protein size, solubility, activity and yield. We present compelling data that the small molecule microarray format can effectively be tailored for use with cellular lysates over-expressing a protein target of biological interest. Furthermore, we have used an optimized protocol to identify two novel, active small molecule inhibitors of the replication checkpoint (SMIRC-1 and SMIRC-2). The enhanced chemosensitivity in p53-negative cell lines supports a plausible role for ATR inhibitors as potentially useful chemotherapeutic agents.

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Journal articles on the topic 'Molecule identification'

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