Academic literature on the topic 'Proteins - Conformation Dynamics'
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Journal articles on the topic "Proteins - Conformation Dynamics"
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Kang, Hyun-Seo, and Michael Sattler. "Capturing dynamic conformational shifts in protein–ligand recognition using integrative structural biology in solution." Emerging Topics in Life Sciences 2, no. 1 (April 20, 2018): 107–19. http://dx.doi.org/10.1042/etls20170090.
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In recent years, a dynamic view of the structure and function of biological macromolecules is emerging, highlighting an essential role of dynamic conformational equilibria to understand molecular mechanisms of biological functions. The structure of a biomolecule, i.e. protein or nucleic acid in solution, is often best described as a dynamic ensemble of conformations, rather than a single structural state. Strikingly, the molecular interactions and functions of the biological macromolecule can then involve a shift between conformations that pre-exist in such an ensemble. Upon external cues, such population shifts of pre-existing conformations allow gradually relaying the signal to the downstream biological events. An inherent feature of this principle is conformational dynamics, where intrinsically disordered regions often play important roles to modulate the conformational ensemble. Unequivocally, solution-state NMR spectroscopy is a powerful technique to study the structure and dynamics of such biomolecules in solution. NMR is increasingly combined with complementary techniques, including fluorescence spectroscopy and small angle scattering. The combination of these techniques provides complementary information about the conformation and dynamics in solution and thus affords a comprehensive description of biomolecular functions and regulations. Here, we illustrate how an integrated approach combining complementary techniques can assess the structure and dynamics of proteins and protein complexes in solution.
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Garaizar, Adiran, Ignacio Sanchez-Burgos, Rosana Collepardo-Guevara, and Jorge R. Espinosa. "Expansion of Intrinsically Disordered Proteins Increases the Range of Stability of Liquid–Liquid Phase Separation." Molecules 25, no. 20 (October 15, 2020): 4705. http://dx.doi.org/10.3390/molecules25204705.
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Proteins containing intrinsically disordered regions (IDRs) are ubiquitous within biomolecular condensates, which are liquid-like compartments within cells formed through liquid–liquid phase separation (LLPS). The sequence of amino acids of a protein encodes its phase behaviour, not only by establishing the patterning and chemical nature (e.g., hydrophobic, polar, charged) of the various binding sites that facilitate multivalent interactions, but also by dictating the protein conformational dynamics. Besides behaving as random coils, IDRs can exhibit a wide-range of structural behaviours, including conformational switching, where they transition between alternate conformational ensembles. Using Molecular Dynamics simulations of a minimal coarse-grained model for IDRs, we show that the role of protein conformation has a non-trivial effect in the liquid–liquid phase behaviour of IDRs. When an IDR transitions to a conformational ensemble enriched in disordered extended states, LLPS is enhanced. In contrast, IDRs that switch to ensembles that preferentially sample more compact and structured states show inhibited LLPS. This occurs because extended and disordered protein conformations facilitate LLPS-stabilising multivalent protein–protein interactions by reducing steric hindrance; thereby, such conformations maximize the molecular connectivity of the condensed liquid network. Extended protein configurations promote phase separation regardless of whether LLPS is driven by homotypic and/or heterotypic protein–protein interactions. This study sheds light on the link between the dynamic conformational plasticity of IDRs and their liquid–liquid phase behaviour.
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Brouhard, Gary J., and Luke M. Rice. "The contribution of αβ-tubulin curvature to microtubule dynamics." Journal of Cell Biology 207, no. 3 (November 10, 2014): 323–34. http://dx.doi.org/10.1083/jcb.201407095.
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Microtubules are dynamic polymers of αβ-tubulin that form diverse cellular structures, such as the mitotic spindle for cell division, the backbone of neurons, and axonemes. To control the architecture of microtubule networks, microtubule-associated proteins (MAPs) and motor proteins regulate microtubule growth, shrinkage, and the transitions between these states. Recent evidence shows that many MAPs exert their effects by selectively binding to distinct conformations of polymerized or unpolymerized αβ-tubulin. The ability of αβ-tubulin to adopt distinct conformations contributes to the intrinsic polymerization dynamics of microtubules. αβ-Tubulin conformation is a fundamental property that MAPs monitor and control to build proper microtubule networks.
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Gormal, Rachel S., Pranesh Padmanabhan, Ravikiran Kasula, Adekunle T. Bademosi, Sean Coakley, Jean Giacomotto, Ailisa Blum, et al. "Modular transient nanoclustering of activated β2-adrenergic receptors revealed by single-molecule tracking of conformation-specific nanobodies." Proceedings of the National Academy of Sciences 117, no. 48 (November 19, 2020): 30476–87. http://dx.doi.org/10.1073/pnas.2007443117.
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None of the current superresolution microscopy techniques can reliably image the changes in endogenous protein nanoclustering dynamics associated with specific conformations in live cells. Single-domain nanobodies have been invaluable tools to isolate defined conformational states of proteins, and we reasoned that expressing these nanobodies coupled to single-molecule imaging-amenable tags could allow superresolution analysis of endogenous proteins in discrete conformational states. Here, we used anti-GFP nanobodies tagged with photoconvertible mEos expressed as intrabodies, as a proof-of-concept to perform single-particle tracking on a range of GFP proteins expressed in live cells, neurons, and small organisms. We next expressed highly specialized nanobodies that target conformation-specific endogenous β2-adrenoreceptor (β2-AR) in neurosecretory cells, unveiling real-time mobility behaviors of activated and inactivated endogenous conformers during agonist treatment in living cells. We showed that activated β2-AR(Nb80) is highly immobile and organized in nanoclusters. The Gαs−GPCR complex detected with Nb37 displayed higher mobility with surprisingly similar nanoclustering dynamics to that of Nb80. Activated conformers are highly sensitive to dynamin inhibition, suggesting selective targeting for endocytosis. Inactivated β2-AR(Nb60) molecules are also largely immobile but relatively less sensitive to endocytic blockade. Expression of single-domain nanobodies therefore provides a unique opportunity to capture highly transient changes in the dynamic nanoscale organization of endogenous proteins.
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Mizutani, Tadashi, and Shigeyuki Yagi. "Linear tetrapyrroles as functional pigments in chemistry and biology." Journal of Porphyrins and Phthalocyanines 08, no. 03 (March 2004): 226–37. http://dx.doi.org/10.1142/s1088424604000210.
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1,19,21,24-tetrahydro-1,19-bilindione is the framework of pigments frequently found in nature, which includes biliverdin IX α, phytochromobilin and phycocyanobilin. 1,19-bilindiones have unique features such as (1) photochemical and thermal cis-trans isomerization, (2) excited energy transfer, (3) chiroptical properties due to the cyclic helical conformation, (4) redox activity, (5) coordination to various metals, and (6) reconstitution to proteins. 1,19-bilindione can adopt a number of conformations since it has exocyclic three double bonds and three single bonds that are rotatable thermally and photochemically. In solution, biliverdin and phycocyanobilin adopt a cyclic helical ZZZ, syn, syn, syn conformation, but other conformations are stabilized depending on the experimental conditions and substituents on the bilin framework. The conformational changes in 1,19-bilindiones are related to the biological functions of a photoreceptor protein, phytochrome. Structural and conformational studies of bilindiones are summarized both in solution and in protein. The conformational changes of bilins can be used for other functions such as a chirality sensor. The bilindiones and the zinc complexes of bilindiones can be employed as a chirality sensor due to the helically chiral structure and the dynamics of racemization of enantiomers. In this paper, we discuss the conformational equilibria and dynamics of bilindiones and its implications in photobiology and materials science.
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Ramirez-Mondragon, Carlos A., Megin E. Nguyen, Jozafina Milicaj, Bakar A. Hassan, Frank J. Tucci, Ramaiah Muthyala, Jiali Gao, Erika A. Taylor, and Yuk Y. Sham. "Conserved Conformational Hierarchy across Functionally Divergent Glycosyltransferases of the GT-B Structural Superfamily as Determined from Microsecond Molecular Dynamics." International Journal of Molecular Sciences 22, no. 9 (April 28, 2021): 4619. http://dx.doi.org/10.3390/ijms22094619.
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It has long been understood that some proteins undergo conformational transitions en route to the Michaelis Complex to allow chemistry. Examination of crystal structures of glycosyltransferase enzymes in the GT-B structural class reveals that the presence of ligand in the active site triggers an open-to-closed conformation transition, necessary for their catalytic functions. Herein, we describe microsecond molecular dynamics simulations of two distantly related glycosyltransferases that are part of the GT-B structural superfamily, HepI and GtfA. Simulations were performed using the open and closed conformations of these unbound proteins, respectively, and we sought to identify the major dynamical modes and communication networks that interconnect the open and closed structures. We provide the first reported evidence within the scope of our simulation parameters that the interconversion between open and closed conformations is a hierarchical multistep process which can be a conserved feature of enzymes of the same structural superfamily. Each of these motions involves of a collection of smaller molecular reorientations distributed across both domains, highlighting the complexities of protein dynamic involved in the interconversion process. Additionally, dynamic cross-correlation analysis was employed to explore the potential effect of distal residues on the catalytic efficiency of HepI. Multiple distal nonionizable residues of the C-terminal domain exhibit motions anticorrelated to positively charged residues in the active site in the N-terminal domain involved in substrate binding. Mutations of these residues resulted in a reduction in negatively correlated motions and an altered enzymatic efficiency that is dominated by lower Km values with kcat effectively unchanged. The findings suggest that residues with opposing conformational motions involved in the opening and closing of the bidomain HepI protein can allosterically alter the population and conformation of the “closed” state, essential to the formation of the Michaelis complex. The stabilization effects of these mutations likely equally influence the energetics of both the ground state and the transition state of the catalytic reaction, leading to the unaltered kcat. Our study provides new insights into the role of conformational dynamics in glycosyltransferase’s function and new modality to modulate enzymatic efficiency.
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Kulkarni, Prakash, Vitor B. P. Leite, Susmita Roy, Supriyo Bhattacharyya, Atish Mohanty, Srisairam Achuthan, Divyoj Singh, et al. "Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma." Biophysics Reviews 3, no. 1 (March 2022): 011306. http://dx.doi.org/10.1063/5.0080512.
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Intrinsically disordered proteins (IDPs) are proteins that lack rigid 3D structure. Hence, they are often misconceived to present a challenge to Anfinsen's dogma. However, IDPs exist as ensembles that sample a quasi-continuum of rapidly interconverting conformations and, as such, may represent proteins at the extreme limit of the Anfinsen postulate. IDPs play important biological roles and are key components of the cellular protein interaction network (PIN). Many IDPs can interconvert between disordered and ordered states as they bind to appropriate partners. Conformational dynamics of IDPs contribute to conformational noise in the cell. Thus, the dysregulation of IDPs contributes to increased noise and “promiscuous” interactions. This leads to PIN rewiring to output an appropriate response underscoring the critical role of IDPs in cellular decision making. Nonetheless, IDPs are not easily tractable experimentally. Furthermore, in the absence of a reference conformation, discerning the energy landscape representation of the weakly funneled IDPs in terms of reaction coordinates is challenging. To understand conformational dynamics in real time and decipher how IDPs recognize multiple binding partners with high specificity, several sophisticated knowledge-based and physics-based in silico sampling techniques have been developed. Here, using specific examples, we highlight recent advances in energy landscape visualization and molecular dynamics simulations to discern conformational dynamics and discuss how the conformational preferences of IDPs modulate their function, especially in phenotypic switching. Finally, we discuss recent progress in identifying small molecules targeting IDPs underscoring the potential therapeutic value of IDPs. Understanding structure and function of IDPs can not only provide new insight on cellular decision making but may also help to refine and extend Anfinsen's structure/function paradigm.
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Westenhoff, Sebastian, Elena Nazarenko, Erik Malmerberg, Jan Davidsson, Gergely Katona, and Richard Neutze. "Time-resolved structural studies of protein reaction dynamics: a smorgasbord of X-ray approaches." Acta Crystallographica Section A Foundations of Crystallography 66, no. 2 (February 18, 2010): 207–19. http://dx.doi.org/10.1107/s0108767309054361.
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Proteins undergo conformational changes during their biological function. As such, a high-resolution structure of a protein's resting conformation provides a starting point for elucidating its reaction mechanism, but provides no direct information concerning the protein's conformational dynamics. Several X-ray methods have been developed to elucidate those conformational changes that occur during a protein's reaction, including time-resolved Laue diffraction and intermediate trapping studies on three-dimensional protein crystals, and time-resolved wide-angle X-ray scattering and X-ray absorption studies on proteins in the solution phase. This review emphasizes the scope and limitations of these complementary experimental approaches when seeking to understand protein conformational dynamics. These methods are illustrated using a limited set of examples including myoglobin and haemoglobin in complex with carbon monoxide, the simple light-driven proton pump bacteriorhodopsin, and the superoxide scavenger superoxide reductase. In conclusion, likely future developments of these methods at synchrotron X-ray sources and the potential impact of emerging X-ray free-electron laser facilities are speculated upon.
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Yang, Jing, Jing Chen, and Zibiao Li. "Structural Basis for the Structure–Activity Behaviour of Oxaliplatin and its Enantiomeric Analogues: A Molecular Dynamics Study of Platinum-DNA Intrastrand Crosslink Adducts." Australian Journal of Chemistry 69, no. 4 (2016): 379. http://dx.doi.org/10.1071/ch15624.
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The discrimination of Pt-GG adducts by mismatch repair proteins, DNA damage-recognition proteins, and translation DNA polymerases was thought to be vital in determining the toxicity, efficacy, and mutagenicity of platinum anti-tumour drugs. Studies on cis-diammine-Pt-GG (from cisplatin and carboplatin) and trans-R,R-diaminocyclohexane (DACH)-Pt-GG indicated that these proteins recognized the differences in conformation and conformational dynamics of Pt-DNA complexes. However, the structural basis of enantiomeric DACH-Pt-GG forms is unclear. Molecular dynamics simulations results presented here reveal that the conformational dynamics between trans-R,R-DACH-Pt-GG, trans-S,S-DACH-Pt-GG, cis-DACH-Pt-GG and undamaged DNA are distinct and depend on the chirality of DACH though their major conformations are similar. Trans-DACH-Pt was found to be energetically favoured over cis-DACH-Pt to form DNA adducts. Moreover, oxaliplatin and its cis-DACH analogues were found to preferentially form hydrogen bonds on the 3′ side of the Pt-GG adduct, whereas the S,S-DACH-Pt preferred the 5′ side. A three-centre hydrogen bond formed between cis1-DACH-Pt and DNA was observed, and the differences in hydrogen bond formation are highly correlated with differences in DNA conformational dynamics. Based on these results, it is suggested that the different bioactivities of oxaliplatin and its enantiomeric analogues were controlled by the difference in hydrogen bonds formation dynamics between DNA and the Pt moiety. Our molecular dynamics approach was demonstrated to be applicable to the study of stereoisomer conformations of platinum-DNA model, thereby suggesting its potential application as a tool for the study and design of new effective platinum-based drugs.
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Li, Haiyan, Zanxia Cao, Guodong Hu, Liling Zhao, Chunling Wang, and Jihua Wang. "Ligand-induced structural changes analysis of ribose-binding protein as studied by molecular dynamics simulations." Technology and Health Care 29 (March 25, 2021): 103–14. http://dx.doi.org/10.3233/thc-218011.
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BACKGROUND: The ribose-binding protein (RBP) from Escherichia coli is one of the representative structures of periplasmic binding proteins. Binding of ribose at the cleft between two domains causes a conformational change corresponding to a closure of two domains around the ligand. The RBP has been crystallized in the open and closed conformations. OBJECTIVE: With the complex trajectory as a control, our goal was to study the conformation changes induced by the detachment of the ligand, and the results have been revealed from two computational tools, MD simulations and elastic network models. METHODS: Molecular dynamics (MD) simulations were performed to study the conformation changes of RBP starting from the open-apo, closed-holo and closed-apo conformations. RESULTS: The evolution of the domain opening angle θ clearly indicates large structural changes. The simulations indicate that the closed states in the absence of ribose are inclined to transition to the open states and that ribose-free RBP exists in a wide range of conformations. The first three dominant principal motions derived from the closed-apo trajectories, consisting of rotating, bending and twisting motions, account for the major rearrangement of the domains from the closed to the open conformation. CONCLUSIONS: The motions showed a strong one-to-one correspondence with the slowest modes from our previous study of RBP with the anisotropic network model (ANM). The results obtained for RBP contribute to the generalization of robustness for protein domain motion studies using either the ANM or PCA for trajectories obtained from MD.
Dissertations / Theses on the topic "Proteins - Conformation Dynamics"
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Ceres, Nicoletta. "Coarse-grain modeling of proteins : mechanics, dynamics and function." Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10030.
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Les protéines sont des molécules flexibles, qui accomplissent une variété de tâches cellulaires à travers des mouvements mécaniques et des changements conformationnels encodés dans leur structure tridimensionnelle. Parmi les approches théoriques qui contribuent à une meilleure compréhension de la relation entre structure, mécanique, dynamique et fonction des protéines, les modèles gros-grains sont un outil très puissant. Ils permettent d’intégrer des informations structurales et dynamiques à un coût computationnel réduit, car le traitement explicite des degrés de liberté moins importants est supprimé. Dans le cadre de cette thèse, des études comparatives rapides de la flexibilité et de la mécanique des protéines ont été menées en se servant du simple modèle gros-grains de Réseau Élastique. La dépendance des résultats de la conformation de départ, ainsi que une liberté dynamique de la chaine principale plutôt limitée, imposée par l’approximation harmonique, nous ont motivé à développer une nouvelle approche, permettant une exploration plus extensive de l’espace conformationnel. Les efforts ont conduit à PaLaCe, modèle gros-grains qui permet des changements majeurs de la structure secondaire, tout en gardant la spécificité de la séquence des acides aminés grâce à une représentation à basse résolution. En utilisant PaLaCe nous avons simulé deux processus impliquant la plasticité protéique: le dépliement du domaine I27 de la protéine musculaire titine et la dynamique à l’équilibre autour de la structure native de deux enzymes homologues adaptées à des températures différentes. Les résultats obtenus concordent avec les données expérimentales et les résultats issus de modèles tout-atom déjà publiés. PaLaCe s’avère donc être un modèle fiable, avec des temps de calcul restreints par rapport aux modèles tout-atome, tout en conservant un bon niveau de détail. Il offre ainsi la possibilité d’effectuer une recherche systématique sur les liens entre mécanique, dynamique et fonction des protéinesProteins are flexible molecules, which accomplish a variety of cellular tasks through mechanical motions and conformational fluctuations encoded in their three-dimensional structure. Amongst the theoretical approaches contributing to a better understanding of the relationship between protein structure, mechanics, dynamics and function, coarse-grain models are a powerful tool. They can be used to integrate structural and dynamic information over broad time and size scales at a low computational cost, achieved by averaging out the less important degrees of freedom. In this work, fast comparative studies of protein flexibility and mechanics have been performed with the simple coarse-grain Elastic Network Model. However, the dependency of the results on the starting conformation, and the rather constrained backbone dynamics imposed by the harmonic approximation, motivated the development of a new approach, for a more extensive exploration of conformational space. These efforts led to the PaLaCe model, designed to allow significant changes in secondary structure, while maintaining residue specificity despite a lower-level resolution. Using PaLaCe, we were able to reproduce two processes involving protein plasticity: the mechanical unfolding of the I27 domain of the giant muscle protein titin and the near-native dynamics of two homologous enzymes adapted to work at different temperatures. Agreement with experimental data and results from published atomistic models demonstrate that PaLaCe is a reliable, sufficiently accurate, but computationally inexpensive approach. It therefore opens the doors for a systematic investigation of the link between protein dynamics/mechanics and function
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Kragelj, Jaka. "Structure and dynamics of intrinsically disordered regions of MAPK signalling proteins." Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENV060/document.
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Les voies de transduction du signal cellulaire permettent aux cellules de répondre aux signaux de l'environnement et de les traiter. Les voies de transduction de kinases MAP (MAPK) sont bien conservées dans toutes les cellules eucaryotes et sont impliquées dans la régulation de nombreux processus cellulaires importants. Les régions intrinsèquement désordonnées (RID), présentes dans de nombreuses MAPK, n'étaient pas encore structurellement caractérisées. Les RID de MAPK sont particulièrement importantes car elles contiennent des motifs de liaison qui contrôlent les interactions entre les protéines MAPK elles-mêmes et aussi entre les protéines MAPK et d'autres protéines contenant les mêmes motifs. La résonance magnétique nucléaire (RMN) en combinaison avec d'autres techniques biophysiques a été utilisée pour étudier les RID de kinase des voies de transduction du signal MAPK. La spectroscopie RMN est bien adaptée pour l'étude des protéines intrinsèquement désordonnées à l'échelle atomique. Les déplacements chimiques et couplages dipolaires résiduels peuvent être utilisés conjointement avec des méthodes de sélection d'ensemble pour étudier la structure résiduelle dans les RID. La relaxation de spin nucléaire nous renseigne sur les mouvements rapides. Des titrations par RMN et des techniques de spectroscopie d'échange peuvent être utilisées pour surveiller la cinétique d'interactions protéine-protéine. Cette étude contribuera à la compréhension du rôle des RID dans les voies de transduction du signal cellulaireProtein signal transduction pathways allow cells respond to and process signals from the environment. A group of such pathways, called mitogen-activated protein kinase (MAPK) signal transduction pathways, is well conserved in all eukaryotic cells and is involved in regulating many important cell processes. Long intrinsically disordered region (IDRs), present in many MAPKs, have remained structurally uncharacterised. The IDRs of MAPKs are especially important as they contain docking-site motifs which control the interactions between MAPK proteins themselves and also between MAPKs and other interacting proteins containing the same motifs. Nuclear magnetic resonance (NMR) spectroscopy in combination with other biophysical techniques was used to study IDRs of MAPKs. NMR spectroscopy is well suited for studying intrinsically disordered proteins (IDPs) at atomic-level resolution. NMR observables, such as for example chemical shifts and residual dipolar couplings, can be used together with ensemble selection methods to study residual structure in IDRs. Nuclear spin relaxation informs us about fast pico-nanosecond motions. NMR titrations and exchange spectroscopy techniques can be used to monitor kinetics of protein-protein interactions. The mechanistic insight into function of IDRs and motifs will contribute to understanding of how signal transduction pathways work
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Murzycki, Jennifer E. "Probing Protein Dynamics Through Mutational and Computational Studies of HIV-1 Protease: A Dissertation." eScholarship@UMMS, 2006. https://escholarship.umassmed.edu/gsbs_diss/166.
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How proteins undergo conformational changes to bind a ligand is one of the most fundamental questions of protein biology. MD simulations provide a useful computational tool for studying the theoretical movements of protein in solution on nanosecond timescales. The results of these simulations can be used to guide experimental design. By correlating the theoretical models with the results of experimental studies, we can obtain a significant amount of information about protein dynamics. This study represents the application of both computational and traditional experimental techniques to study protein dynamics in HIV-1 protease. The results provide a novel mechanism for the conformational changes in proteins and address the role of residues outside the active site in protein dynamics. Additionally, these results are applied to the complex role of non-active site mutations in the development of drug resistance.
Chapter II examines an invariant Thr80 at the apex of the P1 loop of HIV-1, HIV-2, and simian immunodeficiency virus protease. Sequence variability associated with human immunodeficiency virus type 1 (HIV-1) is useful for inferring structural and/or functional constraints at specific residues within the viral protease. Positions that are invariant even in the presence of drug selection define critically important residues for protease function. Three protease variants (T80V, T80N, and T80S) were examined for changes in structure, dynamics, enzymatic activity, affinity for protease inhibitors, and viral infectivity. While all three variants were structurally similar to the wild type, only T80S was functionally similar. T80V significantly decreased the ability of the enzyme to cleave a peptide substrate but maintained infectivity, while T80N abolished both activity and viral infectivity. Additionally, T80N decreased the conformational flexibility of the flap region, as observed by simulations of molecular dynamics. Taken together, these data indicate that HIV-1 protease functions best when residue 80 is a small polar residue and that mutations to other amino acids significantly impair enzyme function, possibly by affecting the flexibility of the flap domain.
Chapter III focuses on residues within the hydrophobic core of each monomer in HIV-1 protease. Many hydrophobic residues located in the core of this dimeric enzyme frequently mutate in patients undergoing protease inhibitor therapy. The mechanism by which these mutations aid the development of drug resistance is not well understood. Using MD simulations, this study suggests that the hydrophobic residues outside the active site facilitate the conformational change that occurs in HIV-1 protease upon binding substrates and inhibitors. In these simulations, the core of each monomer significantly rearranges to assist in the expansion of the active site as hydrophobic core residues slide by each other, exchanging one hydrophobic contact for another. Such hydrophobic sliding may represent a general mechanism by which proteins undergo conformational changes. Mutation of these hydrophobic core residues would alter the packing of the hydrophobic core. Thus, these residues could facilitate drug resistance in HIV-1 protease by altering dynamic properties of HIV-1 protease preferentially affecting the relative affinity for inhibitors versus substrates.
Chapter IV concentrates on a residue in the flap region, Ile54, which is significantly correlated with the development of drug resistance. A series of patient sequences containing the mutation I54A were evaluated for the most frequently occurring co-mutations. I54A was found to occur with mutations that were previously correlated with I54V mutations, including L10I, G48V, and V82A. Based on the results of this evaluation, the binding properties of five variant proteases were investigated: MDI54V, MDRI54A, I54V, I54A, and G48V. MDRI54V and MDRI54Aeach contained the mutations L10I, G48V, and V82A, and either I54V or I54A, respectively. The other variants contained only the mutation indicated. Mutations at Ile54 were able to significantly impact the thermodynamics of binding to saquinavir, amprenavir, and the recently approved darunavir. The magnitude of this impact depended on the presence or absence of other drug resistance mutations, including another mutation in the flap region, G48V. Therefore, while residues 48 and 54 are not in contact with each other, mutations at both sites had a cooperative effect that varies between inhibitors.
The results demonstrate that residues outside the active site of HIV-1 protease are clearly important to enzyme function, possibly through their role in the dynamic properties of protease. Mutations outside the active site of protease that are known to cause drug resistance could alter the conformational flexibility of protease. While the role of protein dynamics in molecular recognition is still not fully understood, the results of this study indicate that altering the dynamic properties of a protein affects its ability to recognize ligands. Therefore, to design better inhibitors we will have to develop a more thorough understanding of protein dynamics.
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Abyzov, Anton. "Nuclear Magnetic Resonance Studies of the Dynamics and Thermodynamics of Intrinsically Disordered Proteins." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAY026/document.
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Les protéines intrinsèquement désordonnées sont des hétéropolymères très flexibles, impliqués dans des activités cellulaires importantes (transduction du signal, reconnaissance moléculaire, traduction etc.), représentant des cibles potentielles de médicaments contre les maladies neurodégénératives et cancers, et dont les modes dynamiques définissent leur fonction biologique. Même si les états conformationnels qu'elles échantillonnent sont relativement bien connus, ce n'est pas le cas des échelles de temps de la dynamique associée. Dans ce travail nous étudions le comportement conformationnel du domaine C-terminal intrinsèquement désordonné de la nucléoprotéine de virus de Sendai (NTAIL), qui interagit avec le domaine PX de la phosphoprotéine. Des études précédentes montrent que le site d'interaction échantillonne un équilibre entre trois hélices discrètes dans l’état libre, et que l’interaction avec PX passe d’abord par la formation d'un pré-complexe, où l’une des conformation hélicoïdales de NTAIL est stabilisée, puis par sa diffusion sur la surface de PX, et enfin sa rétention sur le site de liaison. Cependant, aucun renseignement n'existe sur les échelles de temps de mouvements de la chaine de NTAIL, qui influencent certainement la cinétique de cette interaction, en particulier sa constante de vitesse d’association. Cette protéine de 124 acides aminés représente aussi un système modèle pertinent contenant à la fois de longs domaines dépliés et des régions de structure résiduelle. La mesure d’un vaste et cohérent ensemble de taux de relaxation à différents champs magnétiques et différentes températures nous a permis de caractériser la dynamique de NTAIL à un niveau de détail sans précèdent. A l’aide d’analyse « model-free » étendu, nous avons montré que les composants rapides de la fonction de corrélation nous informent sur les librations. Le mode dominant se situe à des échelles de temps autour d’une nanoseconde et est lié à l’échantillonnage de l’espace de Ramachandran par le squelette peptidique. Enfin, le composant lent (5-25 ns) nous informe sur les mouvements de segments de la chaine peptidique. La description des mouvements intrinsèques des protéines désordonnées et leurs échelles de temps contribuera à notre compréhension du comportement et des fonctions de ces protéinesIntrinsically disordered proteins (IDPs) are highly flexible heteropolymers, implicated in important cellular activities (signal transduction, molecular recognition, transcription, translation, etc.) and representing potential drug targets against cancer and neurodegenerative diseases, whose dynamic modes define their biological function. Although the conformational states sampled by IDPs are relatively well understood, essentially nothing is known about the associated dynamic timescales. In this study we investigate the conformational behavior of the intrinsically disordered C-terminal domain of the nucleoprotein of Sendai virus (NTAIL), which interacts with the PX domain of the phosphoprotein. The interaction site has been shown to sample an equilibrium of discrete helices in the free state, which forms an encounter complex implicating the stabilization of one of the helical conformers upon interaction with PX, prior to diffusing on the surface of PX and engaging in the actual binding site. However, very little is known about the timescales of chain motions, which surely play a role in the interaction kinetics, in particular in terms of the on-rate of the interaction. This 124 amino acid protein also provides a good model system, containing long unfolded domains with chain-like dynamics and regions with residual structure. The measurement of extensive set of coherent relaxation rates at multiple magnetic fields, multiple temperatures and in three different length constructs of the same IDP has allowed us to characterize the dynamic nature of NTAIL in unprecedented detail. By analyzing the relaxation data using extended model-free approach, we show that fast (≤ 50 ps) components of the correlation function report on librational motions. A dominant mode occurs on timescales around one nanosecond, apparently reporting on backbone sampling within Ramachandran sub-states, while a slower component (5-25 ns) reports on segmental dynamics dominated by the chain-like nature of the protein. The ability to delineate intrinsic modes and timescales will improve our understanding of the behavior and function of IDPs
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Link, Justin J. "Ultrafast Protein Conformation Dynamics." The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1230584570.
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Dorywalska, Magdalena. "Conformational dynamics of protein synthesis /." May be available electronically:, 2007. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
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Zang, Chen. "Ultrafast Spectroscopic Study of Protein Conformation Dynamics and Hydration Dynamics." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1299481658.
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Bossa, Cecilia. "Conformational fluctuations in proteins. A molecular dynamics based study." Doctoral thesis, La Sapienza, 2005. http://hdl.handle.net/11573/916821.
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Chen, Wei. "Molecular dynamics simulations of binding, unfolding, and global conformational changes of signaling and adhesion molecules." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28118.
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Thesis (M. S.)--Mechanical Engineering, Georgia Institute of Technology, 2009.Committee Chair: Zhu, Cheng; Committee Member: Harvey, Stephen; Committee Member: Hud, Nicholas; Committee Member: Zamir, Evan; Committee Member: Zhu, Ting.
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Bruce, Neil John. "Investigating protein conformational change via molecular dynamics simulation." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/investigating-protein-conformational-change-via-molecular-dynamics-simulation(17145939-f643-4b23-bbb9-029cf5489c15).html.
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Accumulation and aggregation of the 42-residue amyloid-[beta] (A[beta]) protein fragment, which originates from the cleavage of amyloid precursor protein by beta and gamma secretase, correlates with the pathology of Alzheimer's disease (AD). Possible therapies for AD include peptides based on the A[beta] sequence, and recently identified small molecular weight compounds designed to mimic these, that interfere with the aggregation of A[beta] and prevent its toxic effects on neuronal cells in culture. Here, we use molecular dynamics simulations to compare the mode of interaction of an active (LPFFD) and inactive (LHFFD) [beta]-sheet breaker peptide with an A[beta] fibril structure from solid state NMR studies. We found that LHFFD had a weaker interaction with the fibril than the active peptide, LPFFD, from geometric and energetic considerations, as estimated by the MM/PBSA approach. Cluster analysis and computational alanine scanning identified important ligand-fibril contacts, including a possible difference in the effect of histidine on ligand-fibril [pi]-stacking interactions, and the role of the proline residue establishing contacts that compete with those essential for maintenance of the inter-monomer [beta]-sheet structure of the fibril. Our results show that molecular dynamics simulations can be a useful way to classify the stability of docking sites. These mechanistic insights into the ability of LPFFD to reverse aggregation of toxic A[beta] will guide the redesign of lead compounds, and aid in developing realistic therapies for AD and other diseases of protein aggregation. We have also performed long explicit solvent MD simulations of unliganded amyloid fibril in three putative protonation states, in order to better understand the energetic and mechanical features of the fibril receptor. Over 100 ns MD simulations, the trajectories where fibril has Glu11 and Glu22 side-chains protonated exhibit the least deviation from the initial solid state NMR structures. Free energy calculations on these rajectories suggest that the weakest fibril interface lies in the lateral rather than transverse direction and that there is little dependence on whether the lateral interface is situated at the edge or middle of the fibril. This agrees with recent reported steered molecular dynamics calculations. Secondly, in an effort to improve the ability of atomistic simulation techniques to directly resolve protein tertiary structure from primary amino acid sequence, we explore the use of a molecular dynamics technique based on swarm intelligence, called SWARM-MD, to identify the native states of two peptides, polyalanine and AEK17, as well as Trp-cage miniprotein. We find that the presence of cooperative swarm interactions significantly enhanced the efficiency of molecular dynamics simulations in predicting native conformation. However, it also is evident that the presence of outlying simulation replicas can adversely impact correctly folded replica structures. By slowly removing the swarm potential after folding simulations, the negative effect of the swarm potential can be alleviated and better agreement with experiment obtained.
Books on the topic "Proteins - Conformation Dynamics"
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Livesay, Dennis R. Protein dynamics: Methods and protocols. New York: Humana Press, 2013.
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Subbiah, S. Protein motions. New York: Chaoman & Hall, 1996.
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International Symposium on Structure and Dynamics of Nucleic Acids, Proteins, and Membranes (1986 Riva, Italy). Structure and dynamics of nucleic acids, proteins, and membranes. New York: Plenum Press, 1986.
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Han, Ke-li, Xin Zhang, and Ming-jun Yang, eds. Protein Conformational Dynamics. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-02970-2.
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Rupp, Bernhard. Biomolecular crystallography. New York, NY: Garland Science, 2010.
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Rupp, Bernhard. Biomolecular crystallography. New York, NY: Garland Science, 2010.
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Course on Dynamics and the Problem of Recognition in Biological Macromolecules (2nd 1995 Erice, Italy). Dynamics and the problem of recognition in biological macromolecules. New York: Plenum Press, 1996.
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Xin, Zhang, Ke-li Han, and Ming-jun Yang. Protein Conformational Dynamics. Springer, 2014.
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Xin, Zhang, Ke-Li Han, and Ming-jun Yang. Protein Conformational Dynamics. Springer International Publishing AG, 2016.
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Xin, Zhang, Ke-Li Han, and Ming-jun Yang. Protein Conformational Dynamics. Springer London, Limited, 2014.
Find full textBook chapters on the topic "Proteins - Conformation Dynamics"
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Balasubramaniam, A., S. G. Huang, S. Sheriff, M. Prabhakaran, and V. Renugopalakrishnan. "Solution conformation of neuropeptide Y: 2D NMR and molecular dynamics studies." In Proteins, 79–81. Dordrecht: Springer Netherlands, 1991. http://dx.doi.org/10.1007/978-94-010-9063-6_11.
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Wüthrich, Kurt. "Conformation of Non-Crystalline Proteins Viewed by NMR." In Structure and Dynamics of Nucleic Acids, Proteins, and Membranes, 21–29. Boston, MA: Springer US, 1986. http://dx.doi.org/10.1007/978-1-4684-5308-9_2.
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Choi, Ucheor B., Keith R. Weninger, and Mark E. Bowen. "Immobilization of Proteins for Single-Molecule Fluorescence Resonance Energy Transfer Measurements of Conformation and Dynamics." In Intrinsically Disordered Protein Analysis, 3–20. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-3704-8_1.
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So, Pui-Kin. "Hydrogen–Deuterium Exchange Mass Spectrometry for Probing Changes in Conformation and Dynamics of Proteins." In Methods in Molecular Biology, 159–73. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0892-0_10.
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Mao, Youdong. "Structure, Dynamics and Function of the 26S Proteasome." In Subcellular Biochemistry, 1–151. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-58971-4_1.
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AbstractThe 26S proteasome is the most complex ATP-dependent protease machinery, of ~2.5 MDa mass, ubiquitously found in all eukaryotes. It selectively degrades ubiquitin-conjugated proteins and plays fundamentally indispensable roles in regulating almost all major aspects of cellular activities. To serve as the sole terminal “processor” for myriad ubiquitylation pathways, the proteasome evolved exceptional adaptability in dynamically organizing a large network of proteins, including ubiquitin receptors, shuttle factors, deubiquitinases, AAA-ATPase unfoldases, and ubiquitin ligases, to enable substrate selectivity and processing efficiency and to achieve regulation precision of a vast diversity of substrates. The inner working of the 26S proteasome is among the most sophisticated, enigmatic mechanisms of enzyme machinery in eukaryotic cells. Recent breakthroughs in three-dimensional atomic-level visualization of the 26S proteasome dynamics during polyubiquitylated substrate degradation elucidated an extensively detailed picture of its functional mechanisms, owing to progressive methodological advances associated with cryogenic electron microscopy (cryo-EM). Multiple sites of ubiquitin binding in the proteasome revealed a canonical mode of ubiquitin-dependent substrate engagement. The proteasome conformation in the act of substrate deubiquitylation provided insights into how the deubiquitylating activity of RPN11 is enhanced in the holoenzyme and is coupled to substrate translocation. Intriguingly, three principal modes of coordinated ATP hydrolysis in the heterohexameric AAA-ATPase motor were discovered to regulate intermediate functional steps of the proteasome, including ubiquitin-substrate engagement, deubiquitylation, initiation of substrate translocation and processive substrate degradation. The atomic dissection of the innermost working of the 26S proteasome opens up a new era in our understanding of the ubiquitin-proteasome system and has far-reaching implications in health and disease.
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Barth, Marie, and Carla Schmidt. "Quantitative Cross-Linking of Proteins and Protein." In Methods in Molecular Biology, 385–400. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1024-4_26.
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AbstractCross-linking, in general, involves the covalent linkage of two amino acid residues of proteins or protein complexes in close proximity. Mass spectrometry and computational analysis are then applied to identify the formed linkage and deduce structural information such as distance restraints. Quantitative cross-linking coupled with mass spectrometry is well suited to study protein dynamics and conformations of protein complexes. The quantitative cross-linking workflow described here is based on the application of isotope labelled cross-linkers. Proteins or protein complexes present in different structural states are differentially cross-linked using a “light” and a “heavy” cross-linker. The intensity ratios of cross-links (i.e., light/heavy or heavy/light) indicate structural changes or interactions that are maintained in the different states. These structural insights lead to a better understanding of the function of the proteins or protein complexes investigated. The described workflow is applicable to a wide range of research questions including, for instance, protein dynamics or structural changes upon ligand binding.
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Tan, Yan-Wen, Jeffrey A. Hanson, Jhih-Wei Chu, and Haw Yang. "Confocal Single-Molecule FRET for Protein Conformational Dynamics." In Protein Dynamics, 51–62. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-658-0_3.
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Zheng, Wenjun, and Mustafa Tekpinar. "Analysis of Protein Conformational Transitions Using Elastic Network Model." In Protein Dynamics, 159–72. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-658-0_9.
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Eichinger, Markus, Berthold Heymann, Helmut Heller, Helmut Grubmüller, and Paul Tavan. "Conformational Dynamics Simulations of Proteins." In Computational Molecular Dynamics: Challenges, Methods, Ideas, 78–97. Berlin, Heidelberg: Springer Berlin Heidelberg, 1999. http://dx.doi.org/10.1007/978-3-642-58360-5_4.
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Hills, Ronald D. "Balancing Bond, Nonbond, and Gō-Like Terms in Coarse Grain Simulations of Conformational Dynamics." In Protein Dynamics, 123–40. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-658-0_7.
Full textConference papers on the topic "Proteins - Conformation Dynamics"
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Karplus, M. "Internal dynamics of macromolecules : Simulations of motion in proteins." In International Conference on Ultrafast Phenomena. Washington, D.C.: Optica Publishing Group, 1992. http://dx.doi.org/10.1364/up.1992.thb1.
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The internal motions of proteins will be discussed. Detailed atom-bases simulations of the native conformation space will be supplemented by simplified models for the full conformation space involved in protein folding.
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Xu, Yangqing, and Gang Bao. "Protein Conformational Changes Under Applied Forces." In ASME 1999 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1999. http://dx.doi.org/10.1115/imece1999-0408.
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Abstract Recent studies confirm that stresses, including that due to gravity, tension, compression, pressure, and shear influence cell growth, differentiation, secretion, movement, signal transduction, and gene expression. Yet, little is known about how cells sense the mechanical stresses or deformations, and convert these mechanical signals into biological or biochemical responses. A possible mechno-chemical coupling mechanism involves protein conformational changes under mechanical forces. Our hypothesis is that mechanical forces can cause large changes of the conformation of proteins, which in turn can influence receptor-ligand binding. To test this hypothesis, molecular dynamics simulations and biochemical assays are performed.
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Kazerounian, Kazem, Khalid Latif, Kimberly Rodriguez, and Carlos Alvarado. "ProtoFold: Part I — Nanokinematics for Analysis of Protein Molecules." In ASME 2004 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. ASMEDC, 2004. http://dx.doi.org/10.1115/detc2004-57243.
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Proteins are evolution’s mechanisms of choice. Study of nano-mechanical systems must encompass an understanding of the geometry and conformation of protein molecules. Proteins are open or closed loop kinematic chains of miniature rigid bodies connected by revolute joints. The Kinematics community is in a unique position to extend the boundaries of knowledge in nano biomechanical systems. ProtoFold is a software package that implements novel and comprehensive methodologies for ab initio prediction of the final three-dimensional conformation of a protein, given only its linear structure. In this paper, we present the methods utilized in the kinematics notion and kinematics analysis of protein molecules. The kinematics portion of ProtoFold incorporates the Zero-Position Analysis Method and draws upon other recent advances in robot manipulation theories. We claim that the methodology presented is a computationally superior and more stable alternative to traditional molecular dynamics simulation techniques.
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Dyer, R. Brian, and Timothy P. Causgrove. "Ultrafast Protein Relaxation: Time-Resolved Infrared Studies of Protein Dynamics Triggered by CO Photodissociation from CO Myoglobin." In International Conference on Ultrafast Phenomena. Washington, D.C.: Optica Publishing Group, 1994. http://dx.doi.org/10.1364/up.1994.tub.4.
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A critical feature of the biological function of heme proteins is the direct coupling of protein motion to the process of binding exogenous ligands to the heme. In carbonmonoxymyoglobin (MbCO), a substantial, specific conformational relaxation is associated with the transition from the ligated to the unligated form of the protein. The analogous tertiary structural changes of the monomer heme subunits of hemoglobin ultimately lead to the R→T quaternary structural transition, the allosteric control mechanism of O2 binding efficiency [1]. We have studied these processes on the earliest timescales, using picosecond, time-resolved infrared (TRIR) spectroscopy. It has long been known that infrared spectra in the amide region are sensitive to protein secondary conformation [2]. Recent advances in equipment and techniques have permitted researchers to quantitatively predict secondary structures from infrared spectra [3,4], particularly in the amide I region [4]. Therefore, it is now possible to study protein motion in time-resolved experiments on dynamics and function. The ligation reactions of small molecules such as CO with the heme site of Mb exemplify the mechanisms available to O2. CO is an ideal candidate for initial time-resolved IR experiments in the amide I region because it is easily photolyzed, little geminate recombination [5], and the structure of both MbCO and unligated Mb have been studied by crystallographic methods [6]. TRIR has already been applied to the stretching vibrations of the bound and free CO ligand [7,8]; dynamics of the protein, however, have yet to be probed by TRIR spectroscopy of the protein vibrations. Here we report results on the motions of the protein in response to ligation reactions, probed in the amide I region centered about 1650 cm-1.
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Lim, Manko, Timothy A. Jackson, and Philip A. Anfinrud. "Ultrafast Near-IR Spectroscopy of Carbonmonoxymyoglobin: the Dynamics of Protein Relaxation." In International Conference on Ultrafast Phenomena. Washington, D.C.: Optica Publishing Group, 1992. http://dx.doi.org/10.1364/up.1992.thb3.
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The conformation of a protein often influences its activity, yielding a structure-function relationship. X-ray diffraction studies have shown that the tertiary structures of ligated and deligated myoglobin (Mb) are somewhat different1. Consequently, dissociation of a ligand from Mb triggers a transition between the two tertiary conformations. The potential energy gradient causing this change is developed at the heme; the iron prefers to be in the plane of the porphyrin in ligated Mb but is displaced 0.5 Å from the plane of the porphyrin in deoxy Mb. The dynamics of this conformational transition may influence the dynamics of rebinding ligands, implying that protein dynamics are also functionally important. For example, the dynamics of ligand recombination with Mb following photolysis of MbCO or MbO2 in low-temperature glasses are similar2. In contrast, Mb expurgates CO with far greater efficiency than O2 when photolysis is carried out at biologically important temperatures3. Since protein motion is inhibited at low temperatures, protein relaxation likely accounts for the temperature-dependent difference in the quantum yield of photodissociation. The ability to discriminate against the binding and storage of CO is functionally important as endogenously produced CO would otherwise compete effectively with O2 for binding sites. A steric mechanism for discriminating against the binding of CO, involving the distal histidine, is well known. The dynamics of protein relaxation evidently provide a mechanism for discriminating against the storage of CO. We have investigated the dynamics of protein relaxation in order to probe this mechanism and thereby elucidate the relation between protein dynamics and function.
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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.
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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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Leeson, D. Thorn, and D. A. Wiersma. "Long-Lived Stimulated Photon Echo Studies of Protein and Glass Dynamics." In Spectral Hole-Burning and Related Spectroscopies: Science and Applications. Washington, D.C.: Optica Publishing Group, 1994. http://dx.doi.org/10.1364/shbs.1994.thb1.
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The dynamical behavior of proteins is often interpreted in terms of conformational substates.1 A protein can assume a large number of slightly different structures, separated by conformational barriers. This view is very similar to the description of glass dynamics in terms of two-level systems.2,3 A two-level system (TLS) represents a group of atoms or molecules which can reside in either of two potential energy wells along a conformational coordinate. At very low temperature the TLS can fluctuate between the two potential energy minima through a tunneling process.
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Maghsoodi, Ameneh, Anupam Chatterjee, Ioan Andricioaei, and Noel Perkins. "An Approximate Model of the Dynamics of the Bacteriophage T4 Injection Machinery." In ASME 2016 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2016. http://dx.doi.org/10.1115/detc2016-60281.
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Bacteriophage T4 is one of the most common and complex of the tailed viruses that infect host bacteria using an intriguing contractile tail assembly. Despite extensive progress in resolving the structure of T4, the dynamics of the injection machinery remains largely unknown. This paper contributes a first model of the injection machinery that is driven by elastic energy stored in a structure known as the sheath. The sheath is composed of helical strands of protein that suddenly collapse from an energetic, extended conformation prior to infection to a relaxed, contracted conformation during infection. We employ Kirchhoff rod theory to simulate the nonlinear dynamics of a single protein strand coupled to a model for the remainder of the virus, including the coupled translation and rotation of the head (capsid), neck and tail tube. Doing so provides an important building block towards the future goal of modeling the entire sheath structure which is composed of six interacting helical protein strands. The resulting numerical model exposes fundamental features of the injection machinery including the time scale and energetics of the infection process, the nonlinear conformational change experienced by the sheath, and the contribution of hydrodynamic drag on the head (capsid).
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Cortés, Juan, and Ibrahim Al-Bluwi. "A Robotics Approach to Enhance Conformational Sampling of Proteins." In ASME 2012 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/detc2012-70105.
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Proteins are biological macromolecules that play essential roles in living organisms. Furthermore, the study of proteins and their function is of interest in other fields in addition to biology, such as pharmacology and biotechnology. Understanding the relationship between protein structure, dynamics and function is indispensable for advances in all these areas. This requires a combination of experimental and computational methods, whose development is the object of very active interdisciplinary research. In such a context, this paper presents a technique to enhance conformational sampling of proteins carried out with computational methods such as molecular dynamics simulations or Monte Carlo methods. Our approach is based on a mechanistic representation of proteins that enables the application of efficient methods originating from robotics. The paper explains the generalities of the approach, and gives details on its application to devise Monte Carlo move classes. Results show the good performance of the method for sampling the conformational space of different types of proteins.
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Bao, Gang, and Shannon Stott. "Langevin Dynamics of Hinge-Motion in Proteins." In ASME 2000 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2000. http://dx.doi.org/10.1115/imece2000-2634.
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Abstract Many proteins function in mechanically stressful environments. For example, shear flow in blood vessel may exert a force as high as hundreds of piconewtons on an individual selectin-ligand bond. With such a mechanical force, the receptor (selectin) may deform, thereby altering the conformational match between the receptor and the ligand. Although van der Waals forces, electrostatic and hydrophobic interactions are all important, it is often the 3D geometry local to the binding pocket that dictates the characteristics of the bond between the receptor and the ligand. Good conformational matches lead to strong and long-lasting bonds, whereas poor conformational matches do the converse. it is conceivable that conformational changes in proteins in response to various forces serve as a mechanism for transducing mechanical signals into biochemical responses.
Reports on the topic "Proteins - Conformation Dynamics"
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Hanke, Andreas. Studies of Single Biomolecules, DNA Conformational Dynamics, and Protein Binding. Fort Belvoir, VA: Defense Technical Information Center, July 2008. http://dx.doi.org/10.21236/ada483440.
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Markelz, Andrea G. Terahertz Time Domain Spectroscopy of Conformational Dynamics of Sensor Proteins: Basic Research and Pathogen Sensor Development. Fort Belvoir, VA: Defense Technical Information Center, August 2004. http://dx.doi.org/10.21236/ada426482.
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