Biomolecules' Conformational Changes Studied by Simulations and Enhanced Sampling PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Biomolecules' Conformational Changes Studied by Simulations and Enhanced Sampling PDF full book. Access full book title Biomolecules' Conformational Changes Studied by Simulations and Enhanced Sampling by Yui Tik (Andrew) Pang. Download full books in PDF and EPUB format.
Author: Yui Tik (Andrew) Pang Publisher: Springer ISBN: 9783031706011 Category : Science Languages : en Pages : 0
Book Description
This thesis illuminates the critical roles biomolecules, from small molecules to proteins, play in cellular functionality, particularly highlighting their conformational changes in response to environmental cues or binding events—a cornerstone concept in drug design as well as the manifestations of disease. It explores the conformational flexibility of small molecules and proteins, essential for predicting drug interactions and understanding biological processes. Through advanced molecular dynamics simulations and enhanced sampling techniques, this research offers unprecedented insights into the structural dynamics of three distinct biomolecular systems: the capsid assembly modulator AT130, the passenger domain of pertactin, and the SARS-CoV-2 spike protein. Each system represents a unique facet of biological complexity, underscoring the thesis's contribution to our understanding of biomolecular behavior across various scales. Furthermore, the thesis advances the field by updating the Force Field Toolkit for improved simulation accuracy. This work not only showcases the adaptability and importance of simulation techniques in modern biological research but also paves the way for novel therapeutic strategies by deepening our understanding of biomolecular dynamics.
Author: Yui Tik (Andrew) Pang Publisher: Springer ISBN: 9783031706011 Category : Science Languages : en Pages : 0
Book Description
This thesis illuminates the critical roles biomolecules, from small molecules to proteins, play in cellular functionality, particularly highlighting their conformational changes in response to environmental cues or binding events—a cornerstone concept in drug design as well as the manifestations of disease. It explores the conformational flexibility of small molecules and proteins, essential for predicting drug interactions and understanding biological processes. Through advanced molecular dynamics simulations and enhanced sampling techniques, this research offers unprecedented insights into the structural dynamics of three distinct biomolecular systems: the capsid assembly modulator AT130, the passenger domain of pertactin, and the SARS-CoV-2 spike protein. Each system represents a unique facet of biological complexity, underscoring the thesis's contribution to our understanding of biomolecular behavior across various scales. Furthermore, the thesis advances the field by updating the Force Field Toolkit for improved simulation accuracy. This work not only showcases the adaptability and importance of simulation techniques in modern biological research but also paves the way for novel therapeutic strategies by deepening our understanding of biomolecular dynamics.
Author: Geoffrey M. Gray Publisher: ISBN: Category : Biomolecules Languages : en Pages : 261
Book Description
DNA sequences exist in a prebent conformation compared to nongcognate sequence. This results in a lower deformation energy for the binding of a cognate sequence. Simulations of the C-terminal domain of Cdc37 (chapter 3) in which Y298 was unphosphorylated, phosphorylated and mutated to a phosphomimetic residue, revealed the importance of conformational fluctuations in the regulation of the Hsp90 chaperone cycle. Both the phosphomimetic and phosphorylated systems resulted in the loss of native like contacts and hydrogen bonding for that residue. This resulted in an unfolding of α1 helix and an exposure of an SH2-binding domain. This domain is important for the recognition of client chaperones. Contrastingly, while α1
Author: Srinivasaraghavan Kannan Publisher: ISBN: Category : Languages : en Pages : 140
Book Description
The application of Classical Molecular Dynamics (MD) for the structure prediction of biomolecules is limited by the accuracy of current force fields and the simulation time scale. Biomolecules can adopt several locally stable conformations separated by high energy barriers. Conformational transitions between these stable states can therefore be rare events even on the time scale of tens to hundreds of nanoseconds. Out of the various methods Replica Exchange Molecular Dynamics (Rex MD) is the most successful method to enhance the conformational sampling of biomolecules. But this is limited to only small systems, as the number of replicas required for Rex MD increases with increasing system size. Therefore, during my PhD, I have developed an alternative "Hamiltonian" replica-exchange method that focuses on the biomolecule backbone flexibility by employing a specific biasing potential to promote backbone transitions as a replica coordinate. The aim of this biasing potential is to reduce the energy barriers associated with peptide backbone dihedral transitions. The level of biasing gradually changes along the replicas such that frequent transitions are possible at high levels of biasing and thus the system can escape from getting trapped in local energy minima. This thesis discusses the development of this Biasing Potential Replica Exchange Molecular Dynamics (BP-Rex MD) method in detail. Application of the method to study the conformational sampling of peptides, folding of a mini protein and also for refinement and loop modeling of homology modeled proteins in explicit solvent shows much better sampling of conformational space as compared to the standard MD simulations. One of the main advantages of this BP-Rex MD simulation is that only the biasing potential energy term enters into the exchange probability, meaning that the number of required replicas is expected to scale approximately linearly with the number of included backbone dihedral angles.
Author: Surl-Hee Ahn Publisher: ISBN: Category : Languages : en Pages :
Book Description
Molecular dynamics (MD) simulations are becoming essential tools for many different fields, including biology, chemistry, and materials science, that provide us with a molecular picture of what is really happening at the molecular level for many biophysical phenomena. With MD simulations, we can see how the molecule forms and moves and obtain insight into its mechanisms with higher resolution than experiments. Unfortunately, MD simulations are not without limitations. They are restricted in predictive power because the molecules routinely get "stuck" in metastable states and do not change their conformations for an extended period. Hence, there is currently a huge gap between what MD simulations can model and the timescales of biological processes. Consequently, many methods have been developed for MD simulations over the past few decades to overcome this timescale barrier between MD simulations and biological processes. These are referred to as enhanced sampling methods. We need these methods to overcome the timescale barrier so that critical biophysical phenomena can be observed in a computationally tractable period. Current enhanced sampling methods have demonstrated that they can efficiently obtain thermodynamic and/or kinetic properties. However, there is still a need for an enhanced sampling method that requires little a priori knowledge about the system, is less heuristic, can obtain both thermodynamic and kinetic properties, and can be easily parallelized over the available computational resources for computational efficiency. I will go over several classes of enhanced sampling methods before diving into my new enhanced sampling methods that aim to address the issues mentioned above.
Author: Guohui Li Publisher: Elsevier ISBN: 0323959180 Category : Science Languages : en Pages : 399
Book Description
Chemical Theory and Multiscale Simulation in Biomolecules: From Principles to Case Studies helps readers understand what simulation is, what information modeling of biomolecules can provide, and how to compare this information with experiments. Beginning with an introduction to computational theory for modeling, the book goes on to describe how to control the conditions of modeling systems and possible strategies for time-cost savings in computation. Part Two further outlines key methods, with step-by-step guidance supporting readers in studying and practicing simulation processes. Part Three then shows how these theories are controlled and applied in practice, through examples and case studies on varied applications. This book is a practical guide for new learners, supporting them in learning and applying molecular modeling in practice, whilst also providing more experienced readers with the knowledge needed to gain a deep understanding of the theoretical background behind key methods. Presents computational theory alongside case studies to help readers understand the use of simulation in practice Includes extensive examples of different types of simulation methods and approaches to result analysis Provides an overview of the current academic frontier and research challenges, encouraging creativity and directing attention to current problems
Author: Justin Matthew Spiriti Publisher: ISBN: Category : Adaptive sampling (Statistics) Languages : en Pages : 202
Book Description
Conformational changes in biomolecules often take place on longer timescales than are easily accessible with unbiased molecular dynamics simulations, necessitating the use of enhanced sampling techniques, such as adaptive umbrella sampling. In this technique, the conformational free energy is calculated in terms of a designated set of reaction coordinates. At the same time, estimates of this free energy are subtracted from the potential energy in order to remove free energy barriers and cause conformational changes to take place more rapidly. This dissertation presents applications of adaptive umbrella sampling to a variety of biomolecular systems. The first study investigated the effects of glycosylation in GalNAc2-MM1, an analog of glycosylated macrophage activating factor. It was found that glycosylation destabilizes the protein by increasing the solvent exposure of hydrophobic residues. The second study examined the role of bound calcium ions in promoting the isomerization of a cis peptide bond in the collagen-binding domain of Clostridium histolyticum collagenase. This study determined that the bound calcium ions reduced the barrier to the isomerization of this peptide bond as well as stabilizing the cis conformation thermodynamically, and identified some of the reasons for this. The third study represents the application of GAMUS (Gaussian mixture adaptive umbrella sampling) to on the conformational dynamics of the fluorescent dye Cy3 attached to the 5' end of DNA, and made predictions concerning the affinity of Cy3 for different base pairs, which were subsequently verified experimentally. Finally, the adaptive umbrella sampling method is extended to make use of the roll angle between adjacent base pairs as a reaction coordinate in order to examine the bending both of free DNA and of DNA bound to the archaeal protein Sac7d. It is found that when DNA bends significantly, cations from the surrounding solution congregate on the concave side, which increases the flexibility of the DNA by screening the repulsion between phosphate backbones. The flexibility of DNA on short length scales is compared to the worm-like chain model, and the contribution of cooperativity in DNA bending to protein-DNA binding is assessed.
Author: Prakash Saudagar Publisher: Springer Nature ISBN: 9819920795 Category : Science Languages : en Pages : 287
Book Description
This book describes recent important advancements in protein folding dynamics and stability research, as well as explaining fundamentals and examining potential methodological approaches in protein science. In vitro, in silico, and in vivo method based research of how the stability and folding of proteins help regulate the cellular dynamics and impact cell function that are crucial in explaining various physiological and pathological processes. This book offers a comprehensive coverage on various techniques and related recent developments in the experimental and computational methods of protein folding, dynamics, and stability studies. The book is also structured in such a way as to summarize the latest developments in the fiddle and key concepts to ensure that readers can understand advanced concepts as well as the fundamental big picture. And most of all, fresh insights are provided into the convergence of protein science and technology. Protein Folding Dynamics and Stability is an ideal guide to the field that will be of value for all levels of researchers and advanced graduate students with training in biochemical laboratory research.
Author: Oren M. Becker Publisher: Springer Science & Business Media ISBN: 140203587X Category : Science Languages : en Pages : 225
Book Description
Molecular dynamics simulations have become instrumental in replacing our view of proteins as relatively rigid structures with the realization that they were dynamic systems, whose internal motions play a functional role. Over the years, such simulations have become a central part of biophysics. Applications of molecular dynamics in biophysics range over many areas. They are used in the structure determination of macromolecules with x-ray and NMR data, the modelling of unknown structures from their sequence, the study of enzyme mechanisms, the estimation of ligand-binding free energies, the evaluation of the role of conformational change in protein function, and drug design for targets of known structures. The widespread application of molecular dynamics and related methodologies suggests that it would be useful to have available an introductory self-contained course by which students with a relatively limited background in chemistry, biology and computer literacy, can learn the fundamentals of the field. This Guide to Biomolecular Simulations tries to fill this need. The Guide consists of six chapters which provide the fundamentals of the field and six chapters which introduce the reader to more specialized but important applications of the methodology.
Author: DIWAKAR EDUCATION HUB Publisher: DIWAKAR EDUCATION HUB ISBN: Category : Science Languages : en Pages : 345
Book Description
Graduate Aptitude Test Biotechnology [DBT-PG] Practice Sets 3000 + Question Answer Chapter Wise Book As Per Updated Syllabus Highlights of Question Answer – Covered All 13 Chapters of Latest Syllabus Question As Per Syllabus The Chapters are- 1.Biomolecules-structure and functions 2.Viruses- structure and classification 3.Prokaryotic and eukaryotic cell structure 4.Molecular structure of genes and chromosomes 5.Major bioinformatics resources and search tools 6.Restriction and modification enzyme 7.Production of secondary metabolites by plant suspension cultures; 8.Animal cell culture; media composition and growth conditions 9.Chemical engineering principles applied to biological system 10. Engineering principle of bioprocessing – 11.Tissue culture and its application, In Each Chapter[Unit] Given 230+ With Explanation In Each Unit You Will Get 230 + Question Answer Based on Exam Pattern Total 3000 + Questions Answer with Explanation Design by Professor & JRF Qualified Faculties
Author: Yui Tik (Andrew) Pang
Author: Yui Tik (Andrew) Pang
Author: Xiakun Chu
Author: Geoffrey M. Gray
Author: Srinivasaraghavan Kannan
Author: Surl-Hee Ahn
Author: Guohui Li
Author: Justin Matthew Spiriti
Author: Prakash Saudagar
Author: Oren M. Becker![Graduate Aptitude Test Biotechnology [DBT-PG] Question Bank Book 3000+ Questions With Detail Explanation PDF](https://books.google.com/books/content/images/frontcover/j7_5EAAAQBAJ?fife=w80-h100)
Author: DIWAKAR EDUCATION HUB