Download or read book Molecular Dynamics Simulations of Enforced Functional Protein Motions written by Frauke Gräter and published by . This book was released on 2005 with total page 150 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Functional Domain Motions and Processivity in Bacterial Hyaluronate Lyase written by Harshad Joshi and published by Universal-Publishers. This book was released on 2010-05-12 with total page 175 pages. Available in PDF, EPUB and Kindle. Book excerpt: Processive enzymes are a special class of enzymes which presumably remain attached to their polymeric substrates between multiple rounds of catalysis. Due to this property, the substrate slides along the enzyme and reduces the time for the random diffusional enzyme-substrate encounters thereby increasing the efficiency of these enzymes manifold. Although structural information from many processive enzymes is available, the atomistic details of particularly the substrate sliding process, which is an inherently dynamic process, remain largely unknown. We take first steps to understand the sliding process by investigating a prototypic processive enzyme: Streptococcus Pneumoniae Hyaluronate lyase, a bacterial enzyme that degrades the polysaccharide substrate hyaluronan. Here we have investigated the flexibility of the enzyme as observed from essential dynamics simulations and its relation to the enzyme-substrate interactions by employing several free and enforced molecular dynamics simulations (on sub-microsecond timescale). This way we have identified a coupling between domain motions of the enzyme and the processivity or the sliding phase of the substrate. In the putative mechanism for the substrate translocation phase we observed an energy barrier along the processive direction and it is speculated that this may arise because of the reorientation of the sugar inside the cleft of the protein. This view was supported from the Force probe molecular dynamics simulations and umbrella sampling simulations that were employed to obtain a preliminary free energy profile underlying the mechanism. The observed free energy barrier is low enough to be easily crossed by thermal fluctuations, renderring essential slow collective domain rearrangements as likely rate-limiting factor for the processive cycle. The collective conformational motions of the protein along with particular interactions of individual amino acids may be involved in this translocation phase. Experimental validation along with further computational studies will be useful to understand this complex mechanism.

Download or read book Collective Langevin dynamics of conformational motions in proteins written by Oliver Lange and published by Cuvillier Verlag. This book was released on 2006 with total page 16 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Enforced Large Scale Motions in Proteins written by and published by . This book was released on 2007 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Collective Langevin Dynamics of Conformational Motions in Protein written by and published by Cuvillier Verlag. This book was released on 2006-01-06 with total page 164 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Crystalline Protein Dynamics written by and published by . This book was released on 2005 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding motions in protein crystals is likely to furnish insight into functional protein dynamics and will improve models for refinement against diffraction data. In this thesis, molecular dynamics (MD) simulations of crystalline Staphylococcal nuclease are reported and analysed in terms of fluctuations, correlations, X-ray diffuse scattering, disorder and models of protein motion. Convergence properties of dynamical quantities are determined. The logarithmic dependence on the simulation length of the R factor with the experimental X-ray diffuse scattering, which is determined by the atomic displacement variance-covariance matrix, is extrapolated to predict a convergence time for the whole variance-covariance matrix of approximately 1 microsecond. The dynamical origin of the X-ray diffuse scattering is investigated using models of liquid-like and collective motion. A smooth, nearly-isotropic scattering shell at q=0.28Ang^-1 originates from equal contributions from correlations in nearest-neighbour water molecule dynamics and from internal protein motions, the latter consisting of alpha-helix pitch and inter-beta-strand fluctuations. Superposed on the shell are intense features that originate from a very small number of slowly-varying (>10ns) collective motions. The individual features are assigned to specific collective motions in the protein, and some of these describe potentially functional active-site deformations. The dynamics along each collective mode is described using Brownian dynamics. Modes with frequencies below 0.55THz are overdamped while the majority (98.6%) of modes perfom underdamped vibrations. MD simulations over the pressure range 1bar to 15kbar reveal a qualitative change in the internal protein motions at approximately 4kbar. This change involves the existence of two linear regimes in the mean-square displacement for internal protein motion with a twofold decrease in the slope above 4kbar. The major effect of the pressure increase on the d.

Download or read book Molecular Dynamics Simulation Perspective on the Role of Protein Motions in Allosteric Regulation written by Pattama Wapeesittipan and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Development of Special Molecular Dynamics Based Methods to Accelerate Sampling of Important Protein Motions written by Li Su and published by . This book was released on 2009 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Protein Dynamics Function and Design written by Oleg Jardetzky and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 227 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume is a collection of articles from the proceedings of the International School of Structural Biology and Magnetic Resonance 3rd Course: Protein Dynamics, Function, and Design. This NATO Advance Study Institute was held in Erice at the Ettore Majorana Centre for Scientific Culture on April 16-28, 1997. The aim of the Institute was to bring together experts applyipg different physical methods to problems of macro molecular dynamics-notably x-ray diffraction, NMR and other forms of spectroscopy, and molecular dynamics simulations. Emphasis was placed on those systems and types of problems-such as mechanisms of allosteric control, signal transmission, induced fit to different ligands with its implications for drug design, and the effects of dynamics on structure determination-where a correlation of findings obtained by different methods could shed the most light on the mechanisms involved and stimulate the search for new approaches. The individual articles represent the state of the art in each of the areas cov ered and provide a guide to the original literature in this rapidly developing field. v CONTENTS 1. Determining Structures of ProteinlDN A Complexes by NMR Angela M. Gronenbom and G. Marius Clore 2. Fitting Protein Structures to Experimental Data: Lessons from before Your Mother Was Born . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Jeffrey C. Hoch, Alan S. Stem, and Peter J. Connolly 3. Multisubunit Allosteric Proteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 William N. Lipscomb 4. Studying Protein Structure and Function by Directed Evolution: Examples with Engineered Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Andreas Pliickthun 5. High Pressure Effects on Protein Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Download or read book Protein Dynamics written by and published by . This book was released on 2004 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein dynamics and its relation to protein function is the subject of various studies using both, theoretical and experimental techniques. In this thesis, several aspects of protein dynamics on short timescales are addressed. Motions in the pico- to nanosecond timescale have been experimentally shown to be intimately related to enzyme activity. Incoherent neutron scattering and molecular dynamics simulation are well suited and widely used to study motions on the above timescales. A prominent phenomenon in the context of this observed flexibility-activity relationship is the dynamical transition, i.e. a non-linear increase in atomic fluctuations at a characteristic transition temperature of T_0 ca. 200K. By explicitly incorporating finite resolution of neutron spectrometers in the theoretical analysis of neutron scattering experiments, a novel interpretation of the dynamical transition arises. This alternative 'frequency window' interpretation is shown to reproduce the timescale and temperature dependence of mean-square displacements calculated from MD simulations of a protein in solution. The frequency window interpretation, furthermore, offers an explanation of the experimentally observed shift of T_0 with instrumental resolution. Implications of the new interpretation for the relation between the dynamical transition and enzyme activity are discussed. Molecular dynamics simulations are further used to test the Gaussian approximation implicit in experimental data analysis. Deviations from Gaussian scattering in the calculated spectra for Q^26 Ang^{-2} are shown to be dominated by the distribution of

Download or read book Computer Simulations of Protein Structures and Interactions written by Serafin Fraga and published by Springer Science & Business Media. This book was released on 2013-04-17 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein engineering endeavors to design new peptides and proteins or to change the structural and/or functional characteristics of existing ones for specific purposes, opening the way for the development of new drugs. This work develops in a comprehensive way the theoretical formulation for the methods used in computer-assisted modeling and predictions, starting from the basic concepts and proceeding to the more sophisticated methods, such as Monte Carlo and molecular dynamics. An evaluation of the approximations inherent to the simulations will allow the reader to obtain a perspective of the possible deficiencies and difficulties and approach the task with realistic expectations. Examples from the authors laboratories, as well as from the literature provide useful information.

Download or read book Glassiness and Coupling of Time Scales in Functional Proteins written by Osman Burak Okan and published by . This book was released on 2005 with total page 104 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Folded proteins are functional at relatively elevated temperatures. Below ca. 190-220 K, proteins may still display the same average structure, but lack function due to the absence of large size fluctuations that increase nonlinearly with temperature. In this state, proteins are similar to polymers displaying glassy behavior, with their disordered, amorphous character and heterogeneous dynamics. We provide evidence that the onset of the relevant fluctuations at physiological temperatures occurs with the residue-wise alteration of the slow- nanosecond time scale- motions due to the activity along the envelope of the energy surface defining the folded protein, and the fast -pico second time scale- motions of the activity along the pockets decorating the folded- state envelope. We investigate this time window with spectral analysis methods to map all the relevant modes of fluctuations. Moreover, the temperature dependence of molecular motions are treated within the context of Fractional Brownian Dynamics. The analysis is based on data describing the relaxation phenomena governing the backbone dynamics derived from molecular dynamics simulations of three proteins in the temperature region 140-330K. The shifts in the weights of fundamental dynamical processes are displayed. Implications on controllability of function are discussed.

Download or read book Rigidity Analysis of Protein Structures and Rapid Simulations of Protein Motion written by José Emilio Jiménez Roldán and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: It is a common goal in biophysics to understand protein structural properties and their relationship to protein function. I investigated protein structural properties using three coarse graining methods: a rigidity analysis method First, a geometric simulation method Froda and normal mode analysis as implemented in Elnemo to identify the protein directions of motion. Furthermore, I also compared the results between the coarse graining methods with the results from molecular dynamics and from experiments that I carried out. The results from the rigidity analysis across a set of protein families presented in chapter 3 highlighted two different patterns of protein rigidity loss, i.e. "sudden" and "gradual". It was found that theses characteristic patterns were in line with the rigidity distribution of glassy networks. The simulations of protein motion by merging flexibility, rigidity and normal mode analyses presented in chapter 4 were able to identify large conformational changes of proteins using minimal computational resources. I investigated the use of RMSD as a measure to characterise protein motion and showed that, despite it is a good measure to identify structural differences when comparing the same protein, the use of extensive RMSD better captures the extend of motion of a protein structure. The in-depth investigation of yeast PDI mobility presented in chapter 5 confirmed former experimental results that predicted a large conformational change for this enzyme. Furthermore, the results predicted: a characteristic rigidity distribution for yeast PDI, a minimum and a maximum active site distance and a relationship between the energy cutoff, i.e. the number of hydrogen bonds part of the network of bonds, and protein mobility. The results obtained were tested against molecular dynamics simulations in chapter 6. The MD simulation also showed a large conformational change for yeast PDI but with a slightly different minimum and maximum inter-cysteine distance. Furthermore, MD was able to reveal new data, i.e. the most likely inter-cysteine distance. In order to test the accuracy of the coarse graining and MD simulations I carried out cross-linking experiments to test the minimum inter-cysteine distance predictions. The results presented in chapter 7 show that human PDI minimum distance is below 12Å whereas the yeast PDI minimum distance must be above 12Å as no cross-linking structures where found with the available (12Å long) cross-linkers.

Download or read book Development of a Molecular Dynamics Based Method to Accelerate Sampling of Large Domain Motions in Proteins written by Hongfeng Lou and published by . This book was released on 2006 with total page 450 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Computational Approaches for Understanding Dynamical Systems Protein Folding and Assembly written by and published by Academic Press. This book was released on 2020-03-05 with total page 554 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational Approaches for Understanding Dynamical Systems: Protein Folding and Assembly, Volume 170 in the Progress in Molecular Biology and Translational Science series, provides the most topical, informative and exciting monographs available on a wide variety of research topics. The series includes in-depth knowledge on the molecular biological aspects of organismal physiology, with this release including chapters on Pairwise-Additive and Polarizable Atomistic Force Fields for Molecular Dynamics Simulations of Proteins, Scale-consistent approach to the derivation of coarse-grained force fields for simulating structure, dynamics, and thermodynamics of biopolymers, Enhanced sampling and free energy methods, and much more. Includes comprehensive coverage on molecular biology Presents ample use of tables, diagrams, schemata and color figures to enhance the reader's ability to rapidly grasp the information provided Contains contributions from renowned experts in the field

Download or read book Molecular Simulations and Biomembranes written by Mark S P Sansom and published by Royal Society of Chemistry. This book was released on 2010-08-01 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: The need for information in the understanding of membrane systems has been caused by three things - an increase in computer power; methodological developments and the recent expansion in the number of researchers working on it worldwide. However, there has been no up-to-date book that covers the application of simulation methods to membrane systems directly and this book fills an important void in the market. It provides a much needed update on the current methods and applications as well as highlighting recent advances in the way computer simulation can be applied to the field of membranes and membrane proteins. The objectives are to show how simulation methods can provide an important contribution to the understanding of these systems. The scope of the book is such that it covers simulation of membranes and membrane proteins, but also covers the more recent methodological developments such as coarse-grained molecular dynamics and multiscale approaches in systems biology. Applications embrace a range of biological processes including ion channel and transport proteins. The book is wide ranging with broad coverage and a strong coupling to experimental results wherever possible, including colour illustrations to highlight particular aspects of molecular structure. With an internationally respected list of authors, its publication is timely and it will prove indispensable to a large scientific readership.

Download or read book Rationalization of Protein Conformational Dynamics by Molecular Simulations written by Daniel Alan Barr and published by . This book was released on 2011 with total page 111 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular dynamics (MD) simulations provide a particularly useful approach to understanding conformational change in biomolecular systems. MD simulations provide an atomistic, physics-based description of the motions accessible to biomolecular systems on the pico- to micro-second timescale, yielding important insight into the free energy of the system, the dynamical stability of contacts and the role of correlated motions in directing the motions of the system. In this thesis, I use molecular dynamics simulations to provide molecular mechanisms that rationalize structural, thermodynamic, and mutation data on the interactions between the lac repressor headpiece and its O1 operator DNA as well as the ERK2 protein kinase. I performed molecular dynamics simulations of the lac repressor headpiece - O1 operator complex at the natural angle as well as at under- and overbent angles to assess the factors that determine the natural DNA bending angle. I find both energetic and entropic factors contribute to recognition of the natural angle. At the natural angle the energy of the system is minimized by optimization of protein-DNA contacts and the entropy of the system is maximized by release of water from the protein-DNA interface and decorrelation of protein motions. To identify the mechanism by which mutations lead to auto-activation of ERK2, I performed a series of molecular dynamics simulations of ERK1/2 in various stages of activation as well as the constitutively active Q103A, I84A, L73P and R65S ERK2 mutants. My simulations indicate the importance of domain closure for auto-activation and activity regulation. My results enable me to predict two loss-of-function mutants of ERK2, G83A and Q64C, that have been confirmed in experiments by collaborators. One of the powerful capabilities of MD simulations in biochemistry is the ability to find low free energy pathways that connect and explain disparate structural data on biomolecular systems. An extention of the targeted molecular dynamics technique using constraints on internal coordinates will be presented and evaluated. The method gives good results for the alanine dipeptide, but breaks down when applied to study conformational changes in GroEL and adenylate kinase.