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Author: Dennis N. Bromley
Publisher:
ISBN:
Category :
Languages : en
Pages : 316
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Book Description
The structural dynamics of proteins are integral to protein function; if these structural dynamics are altered by mutation, the function of the protein can be altered as well, potentially resulting in disease. Experimental structure-determination with x-ray crystallography and Nuclear Magnetic Resonance (NMR) can be useful in determining mutant protein structures, but detailed, high-resolution dynamics data can be difficult to ascertain. Molecular Dynamics (MD) simulation is a high temporal- and spatial-resolution in silico method for dynamic protein structure determination. Unfortunately, the data generated by MD simulations can be too large for standard analysis tools. Here I describe a novel visual-analytics tool called DIVE that was specifically created to handle large, structured datasets like those generated by MD simulations. Using DIVE, I analyzed MD simulation-data of disease-associated mutations to the alpha-Tocopherol Transfer Protein (alpha-TTP) and to the p53 tumor suppressor protein. In addition to mutant structural-analysis and characterization, I also used DIVE to develop an algorithm for identifying regions of mutant proteins that are amenable to `rescue', or ligand-mediated stabilization that can suppress the destabilizing effect of mutations. The results of these investigations highlight the utility of big-data, visual-analytics approaches to exploring MD simulation data.
Author: Dennis N. Bromley
Publisher:
ISBN:
Category :
Languages : en
Pages : 316
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Book Description
The structural dynamics of proteins are integral to protein function; if these structural dynamics are altered by mutation, the function of the protein can be altered as well, potentially resulting in disease. Experimental structure-determination with x-ray crystallography and Nuclear Magnetic Resonance (NMR) can be useful in determining mutant protein structures, but detailed, high-resolution dynamics data can be difficult to ascertain. Molecular Dynamics (MD) simulation is a high temporal- and spatial-resolution in silico method for dynamic protein structure determination. Unfortunately, the data generated by MD simulations can be too large for standard analysis tools. Here I describe a novel visual-analytics tool called DIVE that was specifically created to handle large, structured datasets like those generated by MD simulations. Using DIVE, I analyzed MD simulation-data of disease-associated mutations to the alpha-Tocopherol Transfer Protein (alpha-TTP) and to the p53 tumor suppressor protein. In addition to mutant structural-analysis and characterization, I also used DIVE to develop an algorithm for identifying regions of mutant proteins that are amenable to `rescue', or ligand-mediated stabilization that can suppress the destabilizing effect of mutations. The results of these investigations highlight the utility of big-data, visual-analytics approaches to exploring MD simulation data.
Author: Aruna Rajan
Publisher:
ISBN: 9781243754141
Category :
Languages : en
Pages : 102
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Book Description
Microsecond long Molecular Dynamics (MD) trajectories of biomolecular processes are now possible due to advances in computer technology. Soon, trajectories long enough to probe dynamics over many milliseconds will become available. Since these timescales match the physiological timescales over which many small proteins fold, all atom MD simulations of protein folding are now becoming popular. To distill features of such large folding trajectories, we must develop methods that can both compress trajectory data to enable visualization, and that can yield themselves to further analysis, such as the finding of collective coordinates and reduction of the dynamics. Conventionally, clustering has been the most popular MD trajectory analysis technique, followed by principal component analysis (PCA). Simple clustering used in MD trajectory analysis suffers from various serious drawbacks, namely, (i) it is not data driven, (ii) it is unstable to noise and change in cutoff parameters, and (iii) since it does not take into account interrelationships amongst data points, the separation of data into clusters can often be artificial. Usually, partitions generated by clustering techniques are validated visually, but such validation is not possible for MD trajectories of protein folding, as the underlying structural transitions are not well understood. Rigorous cluster validation techniques may be adapted, but it is more crucial to reduce the dimensions in which MD trajectories reside, while still preserving their salient features. PCA has often been used for dimension reduction and while it is computationally inexpensive, being a linear method, it does not achieve good data compression. In this thesis, I propose a different method, a nonmetric multidimensional scaling (nMDS) technique, which achieves superior data compression by virtue of being nonlinear, and also provides a clear insight into the structural processes underlying MD trajectories. I illustrate the capabilities of nMDS by analyzing three complete villin headpiece folding and six norleucine mutant (NLE) folding trajectories simulated by Freddolino and Schulten [1]. Using these trajectories, I make comparisons between nMDS, PCA and clustering to demonstrate the superiority of nMDS. The three villin headpiece trajectories showed great structural heterogeneity. Apart from a few trivial features like early formation of secondary structure, no commonalities between trajectories were found. There were no units of residues or atoms found moving in concert across the trajectories. A flipping transition, corresponding to the flipping of helix 1 relative to the plane formed by helices 2 and 3 was observed towards the end of the folding process in all trajectories, when nearly all native contacts had been formed. However, the transition occurred through a different series of steps in all trajectories, indicating that it may not be a common transition in villin folding. The trajectories showed competition between local structure formation/hydrophobic collapse and global structure formation in all trajectories. Our analysis on the NLE trajectories confirms the notion that a tight hydrophobic core inhibits correct 3-D rearrangement. Only one of the six NLE trajectories folded, and it showed no flipping transition. All the other trajectories get trapped in hydrophobically collapsed states. The NLE residues were found to be buried deeply into the core, compared to the corresponding lysines in the villin headpiece, thereby making the core tighter and harder to undo for 3-D rearrangement. Our results suggest that the NLE may not be a fast folder as experiments suggest. The tightness of the...
Author: Andreas Kukol
Publisher: Humana Press
ISBN: 9781493954919
Category : Science
Languages : en
Pages : 474
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Book Description
Molecular Modeling of Proteins, Second Edition provides a theoretical background of various methods available and enables non-specialists to apply methods to their problems by including updated chapters and new material not covered in the first edition. This detailed volume opens by featuring classical and advanced simulation methods as well as methods to set-up complex systems such as lipid membranes and membrane proteins and continues with chapters devoted to the simulation and analysis of conformational changes of proteins, computational methods for protein structure prediction, usage of experimental data in combination with computational techniques, as well as protein-ligand interactions, which are relevant in the drug design process. Written for the highly successful Methods in Molecular Biology series, chapters include thorough introductions, step-by-step instructions and notes on troubleshooting and avoiding common pitfalls. Update-to-date and authoritative, Molecular Modeling of Proteins, Second Edition aims to aid researchers in the physical, chemical and biosciences interested in utilizing this powerful technology.
Author: Volkhard Helms
Publisher: John Wiley & Sons
ISBN: 3527830529
Category : Science
Languages : en
Pages : 436
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Book Description
Protein Interactions A fundamental guide to the burgeoning field of protein interactions From enzymes to transcription factors to cell membrane receptors, proteins are at the heart of biological cell function. Virtually all cellular processes are governed by their interactions, with one another, with cell bodies, with DNA, or with small molecules. The systematic study of these interactions is called Interactomics, and research within this new field promises to shape the future of molecular cell biology. Protein Interactions goes beyond any existing guide to protein interactions, presenting the first truly comprehensive overview of the field. Edited by two leading scholars in the field of protein bioinformatics, this book covers all known categories of protein interaction, stable as well as transient, as well as the effect of mutations and post-translational modifications on the interaction behavior. Protein Interactions readers will also find: Introductory chapters on protein structure, conformational dynamics, and protein-protein binding interfaces A data-driven approach incorporating machine learning and integrating experimental data into computational models An outlook on the current challenges in the field and suggestions for future research Protein Interactions will serve as a fundamental resource for novice researchers who want a systematic introduction to interactomics, as well as for experienced cell biologists and bioinformaticians who want to gain an edge in this exciting new field.
Author: Timir Tripathi
Publisher: Academic Press
ISBN: 0323902650
Category : Science
Languages : en
Pages : 716
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Book Description
Advances in Protein Molecular and Structural Biology Methods offers a complete overview of the latest tools and methods applicable to the study of proteins at the molecular and structural level. The book begins with sections exploring tools to optimize recombinant protein expression and biophysical techniques such as fluorescence spectroscopy, NMR, mass spectrometry, cryo-electron microscopy, and X-ray crystallography. It then moves towards computational approaches, considering structural bioinformatics, molecular dynamics simulations, and deep machine learning technologies. The book also covers methods applied to intrinsically disordered proteins (IDPs)followed by chapters on protein interaction networks, protein function, and protein design and engineering. It provides researchers with an extensive toolkit of methods and techniques to draw from when conducting their own experimental work, taking them from foundational concepts to practical application. Presents a thorough overview of the latest and emerging methods and technologies for protein study Explores biophysical techniques, including nuclear magnetic resonance, X-ray crystallography, and cryo-electron microscopy Includes computational and machine learning methods Features a section dedicated to tools and techniques specific to studying intrinsically disordered proteins
Author:
Publisher: Academic Press
ISBN: 0128052112
Category : Science
Languages : en
Pages : 400
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Book Description
The Advances in Protein Chemistry and Structural Biology series is an essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins, with each thematically organized volume guest edited by leading experts in a broad range of protein-related topics. Provides cutting-edge developments in protein chemistry and structural biology Chapters are written by authorities in their field Targeted to a wide audience of researchers, specialists, and students
Author:
Publisher: Elsevier
ISBN: 0128114320
Category : Medical
Languages : en
Pages : 3421
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Book Description
Encyclopedia of Bioinformatics and Computational Biology: ABC of Bioinformatics, Three Volume Set combines elements of computer science, information technology, mathematics, statistics and biotechnology, providing the methodology and in silico solutions to mine biological data and processes. The book covers Theory, Topics and Applications, with a special focus on Integrative –omics and Systems Biology. The theoretical, methodological underpinnings of BCB, including phylogeny are covered, as are more current areas of focus, such as translational bioinformatics, cheminformatics, and environmental informatics. Finally, Applications provide guidance for commonly asked questions. This major reference work spans basic and cutting-edge methodologies authored by leaders in the field, providing an invaluable resource for students, scientists, professionals in research institutes, and a broad swath of researchers in biotechnology and the biomedical and pharmaceutical industries. Brings together information from computer science, information technology, mathematics, statistics and biotechnology Written and reviewed by leading experts in the field, providing a unique and authoritative resource Focuses on the main theoretical and methodological concepts before expanding on specific topics and applications Includes interactive images, multimedia tools and crosslinking to further resources and databases
Author: Chandrabose Selvaraj
Publisher: Frontiers Media SA
ISBN: 2832546277
Category : Science
Languages : en
Pages : 179
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Book Description
Everything in a living organism relies on biological macromolecules, which have the role of enzymatic chemical transformations, formation of structures, transportation, catalysis, and regulation of biological processes. They are complex biological structures that require an atomistic understanding. A molecular understanding of biological macromolecules has had a massive impact on the pharmaceutical, biotechnological, and chemical industries. Specifically, new enzymatic structures are being discovered through various experimental and computational methods, by describing an atomistic-level insight into function, mechanism, role in reactions and their inhibition. Those atom-level illustrations are mainly focused through enzyme kinetics, enzyme inhibition, mutational and conformational analysis through quantum mechanical and molecular dynamics methods.
Author: Qiang Cui
Publisher: CRC Press
ISBN: 142003507X
Category : Mathematics
Languages : en
Pages : 448
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Book Description
Rapid developments in experimental techniques continue to push back the limits in the resolution, size, and complexity of the chemical and biological systems that can be investigated. This challenges the theoretical community to develop innovative methods for better interpreting experimental results. Normal Mode Analysis (NMA) is one such technique
Author: Gennady Verkhivker
Publisher: Frontiers Media SA
ISBN: 2889631362
Category :
Languages : en
Pages : 129
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Book Description
Machine learning methods such as neural networks, non-linear dimensionality reduction techniques, random forests and others meet in this research topic with biomolecular simulations. The authors of eight articles applied these methods to analyze simulation results, accelerate simulations or to make molecular mechanics force fields more accurate.
