Academic literature on the topic 'Protein Conformation - Water'
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Journal articles on the topic "Protein Conformation - Water"
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Dubovskii, Peter V., Kira M. Dubova, Gleb Bourenkov, Vladislav G. Starkov, Anastasia G. Konshina, Roman G. Efremov, Yuri N. Utkin, and Valeriya R. Samygina. "Variability in the Spatial Structure of the Central Loop in Cobra Cytotoxins Revealed by X-ray Analysis and Molecular Modeling." Toxins 14, no. 2 (February 18, 2022): 149. http://dx.doi.org/10.3390/toxins14020149.
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Cobra cytotoxins (CTs) belong to the three-fingered protein family and possess membrane activity. Here, we studied cytotoxin 13 from Naja naja cobra venom (CT13Nn). For the first time, a spatial model of CT13Nn with both “water” and “membrane” conformations of the central loop (loop-2) were determined by X-ray crystallography. The “water” conformation of the loop was frequently observed. It was similar to the structure of loop-2 of numerous CTs, determined by either NMR spectroscopy in aqueous solution, or the X-ray method. The “membrane” conformation is rare one and, to date has only been observed by NMR for a single cytotoxin 1 from N. oxiana (CT1No) in detergent micelle. Both CT13Nn and CT1No are S-type CTs. Membrane-binding of these CTs probably involves an additional step—the conformational transformation of the loop-2. To confirm this suggestion, we conducted molecular dynamics simulations of both CT1No and CT13Nn in the Highly Mimetic Membrane Model of palmitoiloleoylphosphatidylglycerol, starting with their “water” NMR models. We found that the both toxins transform their “water” conformation of loop-2 into the “membrane” one during the insertion process. This supports the hypothesis that the S-type CTs, unlike their P-type counterparts, require conformational adaptation of loop-2 during interaction with lipid membranes.
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Greve, Tanja M., Kristine B. Andersen, and Ole F. Nielsen. "Penetration mechanism of dimethyl sulfoxide in human and pig ear skin: An ATR–FTIR and near-FT Raman spectroscopicin vivoandin vitrostudy." Spectroscopy 22, no. 5 (2008): 405–17. http://dx.doi.org/10.1155/2008/109782.
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The penetration mechanism of dimethyl sulfoxide (DMSO) in human skinin vivoandin vitroand pig ear skin in vitro was studied using attenuated total reflectance (ATR) Fourier transform (FT) infrared (IR) and near-FT-Raman spectroscopy. The results showed changes in the conformation of the skin keratins from an α-helical to a β-sheet conformation. These changes were proved to depend on the concentration of free water in the sample as DMSO tended to bind to free water before the protein-bound water was replaced and the protein conformational changes were induced. The induced conformational changes were shown to be completely reversible as the proteins are returned to their original state within 20 h after the treatment with DMSO. The penetration depth of DMSO was shown to depend on the time of exposure – however, after only 15 min DMSO has penetrated thestratum corneum, which is the skin barrier.
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Bridelli, Maria Grazia, and Rosanna Capelletti. "Hydration structure analysis of lysozyme amyloid fibrils by thermally stimulated depolarization currents (TSDC) technique." Spectroscopy 22, no. 2-3 (2008): 165–76. http://dx.doi.org/10.1155/2008/793491.
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Thermally stimulated depolarization currents technique has been employed to investigate the conformation of hen egg white lysozyme in native and amyloid form, in the state of powder at very low hydration level. The technique, able to detect the current generated by thermally activated reorientation of water dipoles previously oriented by an electric field, exploits H2O dipoles, belonging to the solvation shell, as a probe to gain information on the protein conformation.Large differences are detected between the TSDC spectra related to the two different protein conformations, for what concerns the number and position of the main peaks, the native form displaying two peaks, atTM=175 K and atTM=297 K, and the amyloid one, only one at intermediate temperature (TM=235 K). The spectra have been compared with those monitored for poly-L-lysine (MW 80400), as received and prepared in different ways, i.e.α-helix,β-sheet, and coil conformation, respectively. The poly-L-lysine spectra show specific features that can be attributed to water texture around the secondary structure adopted by the macromolecule: the results stress how TSDC technique is a tool of great potential value in the conformational analysis of proteins.
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Dér, A., L. Kelemen, L. Fábián, S. G. Taneva, E. Fodor, T. Páli, A. Cupane, M. G. Cacace, and J. J. Ramsden. "Interfacial Water Structure Controls Protein Conformation." Journal of Physical Chemistry B 111, no. 19 (May 2007): 5344–50. http://dx.doi.org/10.1021/jp066206p.
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Dér, A. "Salts, Interfacial Water and Protein Conformation." Biotechnology & Biotechnological Equipment 22, no. 1 (January 2008): 629–33. http://dx.doi.org/10.1080/13102818.2008.10817524.
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Nagae, Takayuki, Hiroyuki Yamada, and Nobuhisa Watanabe. "High-pressure protein crystal structure analysis of Escherichia coli dihydrofolate reductase complexed with folate and NADP+." Acta Crystallographica Section D Structural Biology 74, no. 9 (September 1, 2018): 895–905. http://dx.doi.org/10.1107/s2059798318009397.
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A high-pressure crystallographic study was conducted on Escherichia coli dihydrofolate reductase (ecDHFR) complexed with folate and NADP+ in crystal forms containing both the open and closed conformations of the M20 loop under high-pressure conditions of up to 800 MPa. At pressures between 270 and 500 MPa the crystal form containing the open conformation exhibited a phase transition from P21 to C2. Several structural changes in ecDHFR were observed at high pressure that were also accompanied by structural changes in the NADP+ cofactor and the hydration structure. In the crystal form with the closed conformation the M20 loop moved as the pressure changed, with accompanying conformational changes around the active site, including NADP+ and folate. These movements were consistent with the suggested hypothesis that movement of the M20 loop was necessary for ecDHFR to catalyze the reaction. In the crystal form with the open conformation the nicotinamide ring of the NADP+ cofactor undergoes a large flip as an intermediate step in the reaction, despite being in a crystalline state. Furthermore, observation of the water molecules between Arg57 and folate elucidated an early step in the substrate-binding pathway. These results demonstrate the possibility of using high-pressure protein crystallography as a method to capture high-energy substates or transient structures related to the protein reaction cycle.
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Biedermannová, Lada, and Bohdan Schneider. "Structure of the ordered hydration of amino acids in proteins: analysis of crystal structures." Acta Crystallographica Section D Biological Crystallography 71, no. 11 (October 27, 2015): 2192–202. http://dx.doi.org/10.1107/s1399004715015679.
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Crystallography provides unique information about the arrangement of water molecules near protein surfaces. Using a nonredundant set of 2818 protein crystal structures with a resolution of better than 1.8 Å, the extent and structure of the hydration shell of all 20 standard amino-acid residues were analyzed as function of the residue conformation, secondary structure and solvent accessibility. The results show how hydration depends on the amino-acid conformation and the environment in which it occurs. After conformational clustering of individual residues, the density distribution of water molecules was compiled and the preferred hydration sites were determined as maxima in the pseudo-electron-density representation of water distributions. Many hydration sites interact with both main-chain and side-chain amino-acid atoms, and several occurrences of hydration sites with less canonical contacts, such as carbon–donor hydrogen bonds, OH–π interactions and off-plane interactions with aromatic heteroatoms, are also reported. Information about the location and relative importance of the empirically determined preferred hydration sites in proteins has applications in improving the current methods of hydration-site prediction in molecular replacement, ab initio protein structure prediction and the set-up of molecular-dynamics simulations.
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Laugwitz, Jeannette M., Haleh H. Haeri, Anette Kaiser, Ulrike Krug, Dariush Hinderberger, Annette G. Beck-Sickinger, and Peter Schmidt. "Probing the Y2 Receptor on Transmembrane, Intra- and Extra-Cellular Sites for EPR Measurements." Molecules 25, no. 18 (September 10, 2020): 4143. http://dx.doi.org/10.3390/molecules25184143.
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The function of G protein-coupled receptors is intrinsically linked to their conformational dynamics. In conjugation with site-directed spin labeling, electron paramagnetic resonance (EPR) spectroscopy provides powerful tools to study the highly dynamic conformational states of these proteins. Here, we explored positions for nitroxide spin labeling coupled to single cysteines, introduced at transmembrane, intra- and extra-cellular sites of the human neuropeptide Y2 receptor. Receptor mutants were functionally analyzed in cell culture system, expressed in Escherichia coli fermentation with yields of up to 10 mg of purified protein per liter expression medium and functionally reconstituted into a lipid bicelle environment. Successful spin labeling was confirmed by a fluorescence assay and continuous wave EPR measurements. EPR spectra revealed mobile and immobile populations, indicating multiple dynamic conformational states of the receptor. We found that the singly mutated positions by MTSL ((1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl) methyl methanesulfonothioate) have a water exposed immobilized conformation as their main conformation, while in case of the IDSL (bis(1-oxyl-2,2,5,5-tetramethyl-3-imidazolin-4-yl) disulfide) labeled positions, the main conformation are mainly of hydrophobic nature. Further, double cysteine mutants were generated and examined for potential applications of distance measurements by double electron–electron resonance (DEER) pulsed EPR technique on the receptor.
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Maciag, Joseph J., Sarah H. Mackenzie, Matthew B. Tucker, Joshua L. Schipper, Paul Swartz, and A. Clay Clark. "Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection." Proceedings of the National Academy of Sciences 113, no. 41 (September 28, 2016): E6080—E6088. http://dx.doi.org/10.1073/pnas.1603549113.
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The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection.
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Martini, Silvia, Claudia Bonechi, Alberto Foletti, and Claudio Rossi. "Water-Protein Interactions: The Secret of Protein Dynamics." Scientific World Journal 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/138916.
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Water-protein interactions help to maintain flexible conformation conditions which are required for multifunctional protein recognition processes. The intimate relationship between the protein surface and hydration water can be analyzed by studying experimental water properties measured in protein systems in solution. In particular, proteins in solution modify the structure and the dynamics of the bulk water at the solute-solvent interface. The ordering effects of proteins on hydration water are extended for several angstroms. In this paper we propose a method for analyzing the dynamical properties of the water molecules present in the hydration shells of proteins. The approach is based on the analysis of the effects of protein-solvent interactions on water protons NMR relaxation parameters. NMR relaxation parameters, especially the nonselective (R1NS) and selective (R1SE) spin-lattice relaxation rates of water protons, are useful for investigating the solvent dynamics at the macromolecule-solvent interfaces as well as the perturbation effects caused by the water-macromolecule interactions on the solvent dynamical properties. In this paper we demonstrate that Nuclear Magnetic Resonance Spectroscopy can be used to determine the dynamical contributions of proteins to the water molecules belonging to their hydration shells.
Dissertations / Theses on the topic "Protein Conformation - Water"
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Lee, Alexis J. "Theoretical Approaches to the Characterization of Water, Aqueous Interfaces, and Improved Sampling of Protein Conformational Changes." ScholarWorks@UNO, 2012. http://scholarworks.uno.edu/td/1511.
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Methods to advance the understanding of water and other aqueous systems are devel- oped. This work falls into three areas: The creation of better interaction potentials for water, improved methods for sampling configurational space, and the applications of these methods to understand systems of interest. Charge transfer has been shown by ab initio methods to be important in the water–water and water–ion interactions. A model for treating charge transfer in liquid water and aqueous systems is presented in this manuscript. The model is called Discrete Charge Transfer (DCT) and is based on the commonly-used TIP4P/2005 model, which represents the charge distribution of water molecules with three charge sites. Such models have been very successful in reproducing many of the physical properties of water. Charge transfer is introduced by transferring a small amount of charge, -0.02e, from the hydrogen bond acceptor to the hydrogen bond donor, as has been indicated by electronic structure calculations. We have parameterized both polarizable and non-polarizable potentials, optimized to include charge transfer. Methods to surmount the obstacles incurred by the introduction of charge transfer, which involve the amount of charge transfer at large distances and implementation into Molecular Dynamics simulation, is presented, along with our results assessing the importance of charge transfer in liquid water and aqueous systems. Also presented is a method for improving eciency of a sampling technique, Replica Exchange, by reducing the number of replicas. The improved method is called Replica Exchange with Driven Scaling (REDS2).
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Boerner, Susann [Verfasser], Erwin [Akademischer Betreuer] Schneider, Michael [Akademischer Betreuer] Beekes, and Walter J. [Akademischer Betreuer] Schulz-Schaeffer. "Probing reaction conditions and cofactors of conformational prion protein changes underlying the autocatalytic self-propagation of different prion strains / Susann Boerner. Gutachter: Erwin Schneider ; Michael Beekes ; Walter J. Schulz-Schaeffer." Berlin : Lebenswissenschaftliche Fakultät, 2014. http://d-nb.info/1054728364/34.
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Lin, Jyh-Home, and 林志宏. "A Water-Packing Method for Applications in Protein 3-D Conformation Computation." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/97072838557001499958.
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Catalini, Sara. "Solvation water role in driving structural conformation and self-assembly of peptides and proteins." Doctoral thesis, 2021. http://hdl.handle.net/2158/1234476.
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“Solvation water role in driving structural conformation and self-assembly of peptides and proteins”, the title of the present thesis, summarizes the objective of my three years PhD course aimed to investigate the relationship existing between the structure of biomolecules in solution and their mutual influence with surrounding water molecules. The three year work has been mainly experimental and principally focused in analyzing the capability of vibrational spectroscopies and some non-linear spectroscopic techniques to disentangle various contributions to solvent-molecule interactions. However to gain a deeper insight in the comprehension of such a complex problem, different types of experimental methods and theoretical modeling have supplemented spectroscopic techniques.
A general survey of UV Resonant Raman (UVRR) spectroscopy and picosecond transient grating (TG) technique is reported in Chapter 2.
The specific interactions of water molecules with glutathione tripeptide dissolved in pure water and water/salts mixtures are investigated experimentally by UVRR spectroscopy and modeled by molecular dynamics simulations. The results are presented in Chapter 3 and focus on the peptide-solvent interactions at the peptide site of glutathione thanks to the high selectivity of UVRR spectroscopy. Spectra are collected and analyzed as a function of concentration, pH, temperature and ion nature. OH stretching and amide modes spectral regions result very sensitive to the variations of the experimental conditions. The output provides a picture of the hydrogen-bonding network around glutathione. The number and the strength of hydrogen bonds increase in the deprotonated form of the tripeptide that exhibits a more marked capacity in decreasing the intermolecular order of water in its hydration shell. Potassium salts and imidazolium based ionic liquids of the halogen series are used to investigate the ions effect on glutathione structure and hydration shell. UVRR spectra present specific features possessing a great dependence on the nature of the anion present in solution rather than that of the cation, suggesting a strong capacity of anions to modify the glutathione structure and its hydration shell. There is a strong evidence that chloride and bromide anions interact at the NH site of glutathione reducing the possibility to form hydrogen bonds with water molecules and making the environment more hydrophobic than in pure water. Instead, iodide anion increases the number of water molecules at the peptide site, creating a strong polar environment. The spectroscopic and computational data are in perfect agreement and their interpretation can be based on the peptide link resonance model. In all the studied solvation environments, a progressive reduction in the strength of hydrogen bond interactions on amide sites is probed upon the increment
of temperature, accompanied by conformational changes involving also the trans-cis isomerization of glutathione.
Chapter 4 deals with the results of the study on self-crowded lysozyme solutions characterized by different degrees of aggregation and networking. Lysozyme has been widely investigated, as a convenient model protein, due to its ability to form amyloid fibrils in acidic conditions at high temperatures. Most of these past studies involved rather diluted samples in which fibril assembly is relatively slow. More rarely the formation of amyloid aggregates was examined in concentrated conditions, despite their relevance in different fields, from cellular biology and medicine to biomaterial and food technologies. In the present study, thermal unfolding and aggregation of highly concentrated (>100 mg/ml) lysozyme solutions at pH=1.8 are investigated. A method is designed to form protein hydrogels in a few hours. Their properties can be easily modulated selecting the curing temperature. The whole gelation process was monitored in situ by Fourier transform infrared (FTIR) spectroscopy assisted by hydrogen/deuterium isotopic exchange, to probe conformational changes and amyloid structuring. Specific molecular conformations are put in relation to thermodynamic properties by calorimetric measurements, to structural information by small angle x-ray and neutron scattering and to viscoelastic properties by means of rheology and TG experiments. This multi-technique approach is necessary in order to obtain a consistent picture on structure-property correlation in self-crowded protein samples. Aggregates constituted by antiparallel cross β-sheet links grow up quickly (less than two hours) within the 45-60 °C temperature range, leading to temperature-dependent quasi-stationary level of amyloid structures, attributed to kinetically trapped oligomers. Upon subsequent cooling, hydrogels develop quickly through the formation of non-specific inter-oligomer contacts. Due to this supramolecular assembly, the hydrogel is transparent, thermo-reversible and rather weak from a mechanical point of view. Lysozyme solutions can be recovered back to a large extent, following a process of oligomer-to-monomer dissociation and refolding. Overall, evidence is given of the possibility of easily forming protein hydrogels in self-crowding conditions constituted by kinetically trapped amyloid oligomers, interconnected by weak interactions. This type of gels might be relevant in different fields, when concentrated protein systems experience denaturing conditions.
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Beauchamp, David L. "The Effect of Salts on the Conformational Stability of Proteins." 2012. http://hdl.handle.net/1993/5306.
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It has long been observed that salts affect proteins in a variety of ways, yet comprehensive explanations for different salt effects are still lacking. In the work presented here, the effect of salts on proteins has been investigated through three different effects: the hydrophobic effect; their conformational stability; the hydrogen bonding network of water in a protein’s hydration shell. UV-vis absorbance and fluorescence spectroscopy were used to monitor changes in two model systems, the phenol-acetate contact pair and the model enzyme ribonuclease t1. It was shown that salts affect the hydrophobicity of the contact pair according to their charge density, induced image charges play an important role in the observed salt-induced increase of ribonuclease t1 stability, and that salts affect ribonuclease t1 activity through modulation of the hydrogen bonds of water in the enzyme’s hydration shell. This work contributes a greater understanding of the effect of salts on proteins.
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Henry, Rowan. "Functional Hydration and Conformational Gating in the D-channel of Cytochrome c Oxidase." Thesis, 2009. http://hdl.handle.net/1807/17514.
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Cytochrome c oxidase couples the reduction of dioxygen to proton pumping against an electrochemical gradient. The D-channel provides the principal uptake pathway for protons. A water chain is thought to mediate the relay of protons through the D-channel, but it is interrupted at N139 in all crystallographic structures. Here, free energy simulations are used to examine the proton uptake pathway in the wild type and in single-point mutants N139V and N139A, where reduction and pumping is compromised. A general approach for the calculation of water occupancy in protein cavities is presented and demonstrates that combining efficient sampling algorithms with long simulation times is required to achieve statistical convergence of equilibrium properties in the protein interior. The relative population of conformational and hydration states of the D-channel is characterized. Results shed light onto the role of N139 in the mechanism of proton uptake and clarify the physical basis for inactive phenotypes.
Books on the topic "Protein Conformation - Water"
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Solvent-dependent flexibility of proteins and principles of their function. Dordrecht: D. Reidel, 1985.
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Frontiers of engineering: Reports on leading-edge engineering from the 2008 symposium. Washington: National Academies Press, 2009.
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Symposium on Frontiers of Engineering (2008 New Mexico). Frontiers of engineering: Reports on leading-edge engineering from the 2008 symposium. Washington: National Academies Press, 2009.
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Symposium on Frontiers of Engineering (2008 New Mexico). Frontiers of engineering: Reports on leading-edge engineering from the 2008 symposium. Washington: National Academies Press, 2009.
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Frontiers of engineering: Reports on leading-edge engineering from the 2007 symposium. Washington, D.C: National Academies Press, 2008.
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Exploring Life Phenomena with Statistical Mechanics of Molecular Liquids. Taylor & Francis Group, 2020.
Find full textBook chapters on the topic "Protein Conformation - Water"
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Lumry, Rufus. "Protein Conformations, “Rack” Mechanisms and Water." In Advances in Chemical Physics, 567–80. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2007. http://dx.doi.org/10.1002/9780470143698.ch39.
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Dyubko, T. S., E. A. Romodanova, V. A. Gavrik, and Yu G. Okladnoy. "Investigation of Induced By low Temperature Water-Soluble Proteins Conformational Rearrangements." In Spectroscopy of Biological Molecules: New Directions, 45–46. Dordrecht: Springer Netherlands, 1999. http://dx.doi.org/10.1007/978-94-011-4479-7_20.
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Haque, E., and B. R. Bhandari. "Effects of Protein Conformational Modifications, Enthalpy Relaxation, and Interaction with Water on the Solubility of Milk Protein Concentrate Powder." In Food Engineering Series, 437–50. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2578-0_38.
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"The Polyproline II Conformation: How Protein Hydration Influences Conformation in Solution." In Water Properties of Food, Pharmaceutical, and Biological Materials, 427–40. CRC Press, 2006. http://dx.doi.org/10.1201/9781420001181-28.
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Chen, Shuai, Yahong Han, Suqing Wang, and Yangchao Luo. "Nanostructured Protein-based Systems." In Bioactive Delivery Systems for Lipophilic Nutraceuticals, 366–91. The Royal Society of Chemistry, 2023. http://dx.doi.org/10.1039/bk9781839165566-00366.
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Protein is a widely available resource in nature that plays important roles in foods. Many proteins can be used to fabricate nanoscale carriers for delivery of bioactive ingredients. This chapter reviewed nanostructured protein-based delivery systems from their microscopic molecular physicochemical principles to macroscopic structural and functional attributes. The structural, physical and chemical properties of protein-based delivery systems were presented in detail, such as molecular conformation, polarity, size, shape, electric charge, water dispersibility, colloidal stability, and so on. Their preparation techniques, including anti-solvent precipitation, pH-driven, electrospray, and gelation methods, to encapsulate bioactive compounds into protein-based nanostructures, were comprehensively reviewed and summarized. Various modifications based on physical, chemical, and enzymatic approaches to improve the physicochemical properties and functional performance of these nano-delivery systems were also discussed. Plant, animal and microbial proteins that have been widely used in nano-delivery systems were classified and described. Finally, the pros and cons and applicable range of nanostructured protein-based delivery systems were discussed and forecasted.
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Dhaval, Patel, Thakor Rajkishan, Mohd Athar, and Prakash Jha. "Role of Ensemble Conformational Sampling Using Molecular Docking & Dynamics in Drug Discovery." In Frontiers in Computational Chemistry: Volume 6, 31–61. BENTHAM SCIENCE PUBLISHERS, 2022. http://dx.doi.org/10.2174/9789815036848122060004.
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Protein interactions with various other macromolecules is a key biological phenomenon for the molecular recognition process leading to various physiological functions. Throughout decades, researchers have proposed various methods for the investigation of such binding mechanism, starting from static, rigid docking to flexible docking approaches. Rational drug designing approaches were improvised by introducing semi- to full-flexibility in the protein-ligand molecular recognition process, conformational dynamics, and binding kinetics and thermodynamics of conserved waters in the binding site. A better understanding of ligand-binding is quintessential to gain more quantitative and accurate information about molecular recognition for drug and therapeutic interventions. To address these issues, Ensemble docking approaches were introduced, which include protein flexibility through a different set of protein conformations either experimentally or with computational simulations i.e., molecular dynamics simulations. MD simulations enable ensemble construction which generates an array of binding site conformations for multiple docking trials of the same protein, though sometimes poorly sampled. To overcome the same, enhanced sampling was introduced. In this chapter, the theoretical background of molecular docking, classical MD simulations, MD-based enhanced sampling methods and hybrid docking-MD based methods are highlighted, demonstrating how protein flexibility has been introduced to optimize and enhance accurate protein-ligand binding predictions. Overall, the evolution of various computational strategies is discussed, from molecular docking to molecular dynamics simulations, to improve the overall drug discovery and development process.
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Akasaka, K., and T. Yamaguchi. "NMR Approaches to the Heat-, Cold-, and Pressure-Induced Unfolding of Proteins." In Biological NMR Spectroscopy. Oxford University Press, 1997. http://dx.doi.org/10.1093/oso/9780195094688.003.0018.
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Proteins are unique at least in two aspects. First, the atoms constituting a protein molecule act highly cooperatively in constructing its unique folded structure. As a result, their conformational transitions also occur in a highly cooperative fashion (often following a two-state transition). Secondly, the free energy balance between the folded (native) and unfolded (denatured) conformers are surprisingly marginal (usually less than 10 kcal/mole protein), despite the fact that interactions of thousands of atoms are involved in the folding. Such unique properties have been acquired by protein molecules through a countless number of random experiments and subsequent selections during the course of evolution of life, so that to our eyes, at present, they look as if they were carefully designed by Nature. It is important to recognize that such random experiments occurred in a dominantly aqueous environment. In order to understand the underlying principles of design as generally as possible, we need, at least, to characterize the factors that contribute to (1) the stability of protein structures, (2) the structural details of the folded and unfolded conformers, and (3) the kinetics of folding and unfolding reactions. In all these, the involvement, of water has crucial importance. NMR can provide unique information not only on aspect (2) above, but on all the above aspects when used under appropriate design. In this presentation, some examples will be shown from our current research. Our daily experience in the kitchen shows that proteins are easily deformed (denatured); a boiled egg can be prepared just by heating to not more than 100°C in water. The easy deformability (which is, in fact, a global conformational transition) in aqueous environment is not merely a matter of interest in a kitchen, but is a quality of design for proteins by Nature. A global conformational transition (unfolding) of a protein molecule occurs even under physiological conditions, although infrequently, as evidenced by hydrogen exchange of peptide NH protons that are completely buried in the folded structure.
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Milhé, C. "Determination by 1H NMR of a Slow Conformational Transition and Hydration Change in the Consensus TATAAT Prsbnow Box." In Biological NMR Spectroscopy. Oxford University Press, 1997. http://dx.doi.org/10.1093/oso/9780195094688.003.0027.
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The conformational dynamics and hydration of a DNA 14-mer containing the consensus Pribnow box sequence TATAAT have been measured using rotating frame T1 measurements and NOESY and ROESY in water. The H2 proton resonances of adenines show fast intermediate exchange behavior which can be attributed to a conformational transition that affects the distances between H2 protons of neighboring adenine residues, both sequential and cross-strand. The relaxation rate constant of the transition was measured at 4000s-1 at 25°C. Bound water close to the H2 proton of adenines was observed with residence times of >lns. At low temperature (5°C), the Pribnow box is in a closed state in which hydration water in the minor groove is tightly bound. At higher temperatures, the conformation opens up as judged by the increase in separation between sequential H2 protons of adenines and water exchanges freely from the minor groove. The conformational transition and the altered hydration pattern may be related to promoter function. The control of gene expression in procaryotes depends on the specific recognition by RNA polymerase of a six base-pair sequence (consensus: TTGACA) located at -35 from the transcription site, and a second one, named the Pribnow box (consensus: TATAAT) at about 10 base-pairs upstream the initiation site (Rosenberg and Court, 1979). It has been shown (Hawley and McClure, 1983) that strong promoters exhibit a high degree of homology with the consensus sequences, separated by an optimum consensus spacer length of 17 base pairs. The strength of a promoter depends on, among other thing, the rate of the initiation of transcription. This rate depends on the product between the thermodynamic and kinetic constants KB and k2 (McClure, 1980). The initial binding of RNA polymerase to the promoter results in the formation of a transcriptionally inactive ‘closed’ complex, characterized by the association constant KB. Isomerization to the active ‘open’ complex then occurs, and is characterized by the first order rate constant k2. Hence, the frequency of transcription initiation depends both on the strength of the polymerase-promoter interaction, and the ease with which this complex can isomerize to the productive state. Both of these events are likely to depend on the physical properties of the promoter.
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Stum, E. A., and T. Gleichmann. "Soaking Techniques." In Crystallization of Nucleic Acids and Proteins. Oxford University Press, 1999. http://dx.doi.org/10.1093/oso/9780199636792.003.0017.
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Once crystals of a macromolecule are obtained there are many circumstances where it is necessary to change the environment in which the macromolecule is bathed. Such changes include the addition of inhibitors, activators, substrates, products, cryo-protectants, and heavy atoms to the bathing solution to achieve their binding to the macromolecule, which may have sufficient freedom to undergo some conformational changes in response to these effectors. In fact, macromolecular crystals have typically a high solvent content which ranges from 27-95% (1, 2). Although, part of this solvent, ‘bound solvent’ (typically 10%) is tightly associated with the protein matrix consisting of both water molecules and other ions that occupy well defined positions in refined crystal structure it can be replaced in soaking experiments, at a slower rate compared to the ‘free solvent’. In this chapter we will consider the relative merits of various methods for modifying crystals, the restraints that the lattice may impose on the macromolecule, and the relative merits of soaking compared to co-crystallization. The size and configuration of the channels within the lattice of macromolecular crystals will determine the maximum size of the solute molecules that may diffuse in. The solvent channels are sufficiently large to allow for the diffusion of most small molecules to any part of the surface of the macromolecule accessible in solution except for the regions involved in crystal contacts, although in some cases lattice forces may hinder conformational changes or rearrangements of the macromolecule in crystal. In other cases, the forces that drive the conformational changes can be sufficient to overcome the constraints imposed by the crystalline lattice leading to the disruption of intermolecular and crystal contacts resulting in the cracking and dissolution of the crystals. Some lattices may be more flexible and capable of accommodating conformational changes, and while crystals may crack initially, they may subsequently anneal into a new rearrangement and occasionally improve their crystallinity. In general small changes are easily accommodated and many macromolecules maintain their activity in the crystalline state. This is exploited in time-resolved crystallography to obtain structural information of transition states of enzymes.
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Northrop, Dexter B. "Steady-State Enzyme Kinetics at High Pressure." In High Pressure Effects in Molecular Biophysics and Enzymology. Oxford University Press, 1996. http://dx.doi.org/10.1093/oso/9780195097221.003.0018.
Full textAbstract:
Pressure effects on enzyme-catalyzed reactions were traditionally interpreted within a simplistic kinetic mechanism in which the transition state presented the highest energy barrier, and the chemical transformation of substrate to product was considered to be a singular, rate-limiting step. This was also true of isotope effects on enzyme-catalyzed reactions, but extensive isotopic studies have led to the conclusion that this transition state is rarely the highest barrier. Rather, the release of products (or the conformational change preceding product release) is usually the slowest step, often accompanied by several other partially ratelimiting steps. Thus, our interpretations of pressure effects must be shifted accordingly. Values attributed to AV‡ have been determined for more than 50 enzymes, more of them with a positive sign than negative, and most in the range of 20 to 40 ml mol–1 but these may or may not have anything to do with the activation volume associated with the transition state. Volume changes specifically associated with the binding of ligands to enzymes have been reported as well, including some very large values, as high as ΔV = 85 ml mo–1. Kinetically, these equilibrium pressure effects also originate in conformational changes because water is not very compressible; hence, rates of diffusion to and from enzymes are virtually unaffected by pressure. Much larger changes, as high as ΔV = –391 mi mo–1, have been observed during disaggregation and denaturation of enzymes. Thus, while it is possible for pressure effects to be expressed on every step of an enzymatic reaction, and to cause denaturation as well, making kinetic data from pressure effects hopelessly complex and uninterpretable, it appears likely that the most significant pressure effects will be expressed on conformational changes associated with product dissociations, without much kinetic complexity. This makes sense from another point of view—that the largest volume changes are probably on solvation equilibria during ligand binding and protein folding. Pressure effects on isotope effects have the potential of specifically identifying whether or not a volume change occurs upon attaining the transition state. With the exception of hydrogen tunneling, intrinsic isotope effects are independent of pressure.
Conference papers on the topic "Protein Conformation - Water"
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Jewel, Yead, Prashanta Dutta, and Jin Liu. "Coarse-Grained Molecular Dynamics Simulations of Sugar Transport Across Lactose Permease." In ASME 2015 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2015. http://dx.doi.org/10.1115/imece2015-52337.
Full textAbstract:
Sugar (one of the critical nutrition elements for all life forms) transport across the cell membranes play essential roles in a wide range of living organism. One of the most important active transport (against the sugar concentration) mechanisms is facilitated by the transmembrane transporter proteins, such as the Escherichia coli lactose permease (LacY) proteins. Active transport of sugar molecules with LacY proteins requires a proton gradient and a sequence of complicated protein conformational changes. However, the exact molecular mechanisms and the protein structural information involved in the transport process are largely unknown. All atom atomistic simulations are able to provide full details but are limited to relative small length and time scales due to the computational cost. The protein conformational changes during sugar transport across LacY are large scale structural reorganization and inaccessible to all atom simulations. In this work, we investigate the molecular mechanisms and conformational changes during sugar transport using coarse-grained molecular dynamics (CGMD) simulations. In our coarse-grained force field, we follow the procedures developed by Han et al. [1, 2], in which the protein model is united-atom based and each heavy atom together with the attached hydrogen atoms is represented by one site, then the protein force filed is coupled with the MARTINI [3] water and lipid force fields. This hybrid force field takes the advantage of the efficiency of MARTINI force field for the environment (water and lipid), while retaining the detailed conformational information for the proteins. Specifically, we develop the new force fields for interactions between sugar molecules and protein by matching the potential of mean force between all-atom and coarse-grained models. Then we validate our force field by comparing the potential of mean force for a glucose interaction with a carbohydrate binding protein from our new force field, with the results from all atom simulations. After validation, we implement the force field for sugar transport across LacY proteins. Through our simulations we are able to capture the formation/breakage of the important hydrogen bonds and salt bridges, which are crucial to the overall conformational changes of LacY.
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Chen, Kok Hao, and Jong Hyun Choi. "DNA Oligonucleotide-Templated Nanocrystals: Synthesis and Novel Label-Free Protein Detection." In ASME 2009 International Mechanical Engineering Congress and Exposition. ASMEDC, 2009. http://dx.doi.org/10.1115/imece2009-11958.
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Semiconductor and magnetic nanoparticles hold unique optical and magnetic properties, and great promise for bio-imaging and therapeutic applications. As part of their stable synthesis, the nanocrystal surfaces are usually capped by long chain organic moieties such as trioctylphosphine oxide. This capping serves two purposes: it saturates dangling bonds at the exposed crystalline lattice, and it prevents irreversible aggregation by stabilizing the colloid through entropic repulsion. These nanocrystals can be rendered water-soluble by either ligand exchange or overcoating, which hampers their widespread use in biological imaging and biomedical therapeutics. Here, we report a novel scheme of synthesizing fluorescent PbS and magnetic Fe3O4 nanoparticles using DNA oligonucleotides. Our method of PbS synthesis includes addition of Na2S to the mixture solution of DNA sequence and Pb acetate (at a fixed molar ratio of DNA/S2−/Pb2+ of 1:2:4) in a standard TAE buffer at room temperature in the open air. In the case of Fe3O4 particle synthesis, ferric and ferrous chloride were mixed with DNA in DI water at a molar ratio of DNA/Fe2+/Fe3+ = 1:4:8 and the particles were formed via reductive precipitation, induced by increasing pH to ∼11 with addition of ammonium hydroxide. These nanocrystals are highly stable and water-soluble immediately after the synthesis, due to DNA termination. We examined the surface chemistry between oligonucleotides and nanocrystals using FTIR spectroscopy, and found that the different chemical moieties of nucleobases passivate the particle surface. Strong coordination of primary amine and carbonyl groups provides the chemical and colloidal stabilities, leading to high particle yields (Figure 1). The resulting PbS nanocrystals have a distribution of 3–6 nm in diameter, while a broader size distribution is observed with Fe3O4 nanoparticles as shown in Figure 1b and c, respectively. A similar observation was reported with the pH change-induced Fe3O4 particles of a bimodal size distribution where superparamagnetic and ferrimagnetic magnetites co-exist. In spite of the differences, FTIR measurements suggest that the chemical nature of the oligonucleotide stabilization in this case is identical to the PbS system. As a particular application, we demonstrate that aptamer-capped PbS QD can detect a target protein based on selective charge transfer, since the oligonucleotide-templated synthesis can also serve the additional purpose of providing selective binding to a molecular target. Here, we use thrombin and a thrombin-binding aptamer as a model system. These QD have diameters of 3∼6 nm and fluoresce around 1050 nm. We find that a DNA aptamer can passivate near IR fluorescent PbS nanocrystals, rendering them water-soluble and stable against aggregation, and retain the secondary conformation needed to selectively bind to its target, thrombin, as shown in Figure 2. Importantly, we find that when the aptamer-functionalized nanoparticles binds to its target (only the target), there is a highly systematic and selective quenching of the PL, even in high concentrations of interfering proteins as shown in Figure 3a and b. Thrombin is detected within one minute with a detection limit of ∼1 nM. This PL quenching is attributed to charge transfer from functional groups on the protein to the nanocrystals. A charge transfer can suppress optical transition mechanisms as we observe a significant decrease in QD absorption with target addition (Figure 3c). Here, we rule out other possibilities including Forster resonance energy transfer (FRET) and particle aggregation, because thrombin absorb only in the UV, and we did not observe any significant change in the diffusion coefficient of the particles with the target analyte, respectively. The charge transfer-induced photobleaching of QD and carbon nanotubes was observed with amine groups, Ru-based complexes, and azobenzene compounds. This selective detection of an unlabeled protein is distinct from previously reported schemes utilizing electrochemistry, absorption, and FRET. In this scheme, the target detection by a unique, direct PL transduction is observed even in the presence of high background concentrations of interfering negatively or positively charged proteins. This mechanism is the first to selectively modulate the QD PL directly, enabling new types of label free assays and detection schemes. This direct optical transduction is possible due to oligonucleotidetemplated surface passivation and molecular recognition. This chemistry may lead to more nanoparticle-based optical and magnetic probes that can be activated in a highly chemoselective manner.
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Chang, Liuyi, and Jiajia Rao. "The role of conformational state of pea protein fractions on the oil/water dynamic adsorption, rheological interfacial properties and emulsifying properties." In 2022 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2022. http://dx.doi.org/10.21748/zjao7478.
Full textAbstract:
Recently, the utilization of pea protein is on the rise because of its low price and nutritional benefits. However, the application of pea proteins is still limited by its functional properties as compared to other plant proteins due to insufficient research, especially in structure-functionality relationship among individual pea protein fractions. Regarding the functional properties, emulsifying properties is one of the important functional properties of protein. It is well established that the emulsifying properties of protein is affected by protein composition, structural properties and environmental factors. As such, the aim of this study was to investigate the impact of environmental pHs (3, 7, 9) and different salt concentrations (20 mM, 200 mM) on protein structure, kinetic adsorption and rheological interfacial properties of pea protein fractions (globulin, legumin, vicilin and albumin) at the oil/water interface, and then to research its relationship with emulsifying properties. The results showed that the addition of NaCl had a greater impact when compared to pH for all tested pea protein fractions in a number of direction. For instance, the secondary structure of the protein was changed, the ability of the protein to increase the interfacial pressure (π) was reduced. Consequently, the emulsifying capacity was also decreased. With regard to the fraction effect, legumin subunit had higher emulsifying stability when compared to vicilin. For example, the particle size of legumin stabilized emulsion increased slightly, but that of vicilin stabilized emulsion droplet increased dramatically (from 4.78 to 19.43 μm) after 24 h storage at pH 3. This phenomenon might be attributed to the higher macromolecular interactions of vicilin at oil/water interface (e.g., the slopes of E- π plots were 2.18 legumin vs 3.19 vicilin). The research results could provide valuable information on molecular mechanism of emulsifying properties of pea protein fractions.
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Peterson, Kristen A., Jeffrey R. Hill, A. Tokmakoff, B. Sauter, D. Zimdars, Dana D. Dlott, and M. D. Fayer. "Vibrational Dynamics at the Active Site of Myoglobin: Picosecond Infrared Free-electron Laser Experiments." In International Conference on Ultrafast Phenomena. Washington, D.C.: Optica Publishing Group, 1994. http://dx.doi.org/10.1364/up.1994.pd.4.
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Vibrational lifetimes of CO bound to myoglobin and to a water-soluble Fe:porphyrin were measured by ps infrared experiments. Vibrational relaxation rates are found to depend on protein conformational substate and porphyrin substitution. We have made direct measurements of molecular energy transfer at the active site of a protein using intense tunable mid-IR pulses from a free-electron laser to measure the loss of vibrational energy from CO bound to a bare water soluble heme and CO bound to the active sites of different conformational substates of myoglobin. Vibrational relaxation rates are found to depend on protein conformational substate and porphyrin substitution.
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Hinkov, Borislav, Florian Pilat, Laurin Lux, Patricia L. Souza, Mauro David, Andreas Schwaighofer, Bettina Baumgartner, et al. "A Monolithic Lab-on-a-Chip for Real Time Liquid Spectroscopy." In Optical Sensors. Washington, D.C.: Optica Publishing Group, 2022. http://dx.doi.org/10.1364/sensors.2022.stu5c.5.
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We present a monolithic mid-infrared lab-on-a-chip for sensitive and selective real-time liquid spectroscopy. Beyond state-of-the-art operation of our fingertip-sized devices is demonstrated by in-situ reaction-monitoring of thermally-induced protein-conformational changes and by dynamical residual-water analysis in solvents.
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Gallegos, C., M. C. Sánchez, A. Guerrero, and J. M. Franco. "Effect of Process Parameters on the Rheological Properties of O/W Emulsions." In ASME 1996 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1996. http://dx.doi.org/10.1115/imece1996-0242.
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Abstract An overview of the effects that different processing conditions have on the rheology and droplet size distribution of o/w emulsions containing different macromolecular and low molecular weight emulsifiers is presented. The processing variables studied were emulsification time, agitation speed, temperature of emulsification, previous thermal treatment of the continuous phase and type of device used. Generally, an increase in the energy input during emulsification yields lower values of the mean droplet size, but does not always improve the viscoelastic properties of the emulsion. Thus, the bulk rheology of the emulsions may also be influenced by the phase behavior of the surfactant-water system, or by changes in the structural conformation of proteins. These influences are easily changed by modifying the temperature of emulsification or by a pre-emulsification thermal treatment of the continuous phase, which affect the microstructure of the emulsion and, subsequently, its linear viscoelastic behavior.
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Mukherjee, Rudranarayan M., Paul Crozier, and Kurt S. Anderson. "Multibody Molecular Dynamics II: Applications and Results." In ASME 2007 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. ASMEDC, 2007. http://dx.doi.org/10.1115/detc2007-35561.
Full textAbstract:
This is the second paper in a series of two papers on using multibody dynamics algorithms and methods for coarse grained molecular dynamics simulations. In the previous paper, the theoretical discussions on this topic have been presented. This paper presents results obtained from simulating several biomolecular and bulk materials using multibody dynamics algorithms. The systems studied include water boxes, alkane chains, alanine dipeptide and carboxyl terminal fragments of Calmodulin, Ribosomal, and Rhodopsin proteins. The atomistic representations of these systems include several thousand degrees of freedom and results of several nano-second simulations of these systems are presented. The stability and validity of the simulations are studied through conservation of energy, thermodynamics properties and conformational analysis. In these simulations, a speed up of an order of magnitude is realized for conservative error bounds. A discussion is presented on the open-source software developed to facilitate future research using multibody dynamics with molecular dynamics.