Computational Approaches to Protein Dynamics

Description

The Latest Developments on the Role of Dynamics in Protein Functions

Computational Approaches to Protein Dynamics: From Quantum to Coarse-Grained Methods presents modern biomolecular computational techniques that address protein flexibility/dynamics at all levels of theory. An international contingent of leading researchers in chemistry, physics, and biology show how these advanced methods provide insights into dynamic aspects of biochemical processes. A particular focus is on intrinsically disordered proteins (IDPs), which lack a well-defined three-dimensional structure and function as dynamic ensembles.

The book covers a wide spectrum of dynamics, from electronic structure-based to coarse-grained techniques via multiscaling at different levels. After an introduction to dynamics and historical overview of basic methodologies, the book addresses the following issues:

• Is there a quantitative relationship between enzymatic catalysis and protein dynamics?
• Which are the functionally relevant motions of proteins?
• How can structural properties and partner recognition mechanisms of IDPs be simulated?
• How can we speed up molecular dynamics?
• How can we describe conformational ensembles by the synergistic effort of computations and experiments?

While dynamics is now considered essential for interpreting protein action, it is not yet an integral component in establishing structure–function relationships of proteins. Helping to reshape this classical view in biochemistry, this groundbreaking book explores advances in computational methodology and contributes to the new, ensemble way of studying proteins.

Table of Contents

1. Introduction
   1. Dynamics: A Key to Protein Function Mónika Fuxreiter
2. Enzymatic Catalysis: Multiscale QM/MM Calculations
   1. Adaptive and Accurate Force-Based QM/MM Calculations Noam Bernstein, Iván Solt, Letif Mones, Csilla Várnai, Steven A. Winfield, and Gábor Csányi
   2. Conformational and Chemical Landscapes of Enzyme Catalysis Alexandra T.P. Carvalho, Fernanda Duarte, Konstantinos Vavitsas, and Shina Caroline Lynn Kamerlin
   3. Interplay between Enzyme Function and Protein Dynamics: A Multiscale Approach to the Study of the NAG Kinase
   4. Family and Two Class II Aldolases Enrique Marcos, Melchor Sanchez-Martinez, and Ramon Crehuet
3. Protein Motions: Flexibility Analysis
   1. Simplified Flexibility Analysis of Proteins Yves-Henri Sanejouand
4. Approaches to Intrinsically Disordered Proteins
   1. ABSINTH Implicit Solvation Model and Force Field Paradigm for Use in Simulations of Intrinsically Disordered Proteins Anuradha Mittal, Rahul K. Das, Andreas Vitalis, and Rohit V. Pappu
   2. Intrinsically Disordered Protein: A Thermodynamic Perspective Jing Li, James O. Wrabl, and Vincent J. Hilser
   3. Long Molecular Dynamics Simulations of Intrinsically Disordered Proteins Reveal Preformed Structural Elements for Target Binding Elio Cino, Mikko Karttunen, and Wing-Yiu Choy
   4. Multiscale Simulations of Large Conformational Changes of Disordered and Ordered Proteins Induced by Their Partners Yong Wang, Xiakun Chu, and Jin Wang
   5. Coarse-Grained Simulation of Intrinsically Disordered Proteins David de Sancho, Christopher M. Baker, and Robert B. Best
   6. Natural and Directed Evolution of Intrinsically Disordered Proteins Tali H. Reingewertz and Eric J. Sundberg
5. Large-Scale Dynamics
   1. Discrete Molecular Dynamics: Foundations and Biomolecular Applications Pedro Sfriso, Agustí Emperador, Josep Lluis Gelpí, and Modesto Orozco
6. Ensemble Methods
   1. Use of Ensemble Methods to Describe Biomolecular Dynamics by Small Angle X-Ray Scattering Giancarlo Tria, Dmitri I. Svergun, and Pau Bernadó
   2. Bridging Experiments and Simulations: Structure Calculations with a Dynamical Touch Florian Heinkel, Alexander Cumberworth, and Jörg Gsponer
7. Index

Editor Description

Mónika Fuxreiter is head of the Laboratory of Protein Dynamics in the Department of Biochemistry and Molecular Biology at the University of Debrecen. She received her MSc and PhD from the Eötvös Loránd University of Sciences, and was a postdoctoral fellow at the University of Southern California under Arieh Warshel. Dr. Fuxreiter has 20 years of experience working on state-of-the-art approaches for biological systems, including partner recognition mechanisms of IDPs and unique regulatory mechanisms of fuzzy complexes and relationships to context-dependence.