Molecular Dynamics Simulations to Study Protein Folding and Unfolding

Abstract

Originally published in: Protein Folding Handbook. Part II. Edited by Johannes Buchner and Thomas Kiefhaber. Copyright © 2005 Wiley‐VCH Verlag GmbH & Co. KGaA Weinheim. Print ISBN: 3‐527‐30784‐2 The sections in this article are Introduction Molecular Dynamics Simulations of Peptides and Proteins Folding of Structured Peptides Reversible Folding and Free Energy Surfaces Non‐Arrhenius Temperature Dependence of the Folding Rate Denatured State and Levinthal Paradox Folding Events of Trp‐cage Unfolding Simulations of Proteins High‐temperature Simulations Biased Unfolding Forced Unfolding Determination of the Transition State Ensemble MD Techniques and Protocols Techniques to Improve Sampling Replica Exchange Molecular Dynamics Methods Based on Path Sampling MD with Restraints Distributed Computing Approach Implicit Solvent Models versus Explicit Water Conclusion

Effects of force fields on the conformational and dynamic properties of amyloid β(1‐40) dimer explored by replica exchange molecular dynamics simulations

“…The use of robust statistical methods as outlined in the supporting materials have allowed us to systematically compare and document the effects of force field selection on the sampled conformational space of the inherently disordered protein Aβ(1–40) dimer in water at physiological temperature (310 K). Although, atomistic MD simulations have even been able to accurately predict the folded state of globular proteins, intermediate states are not consistent with experimental data and simulations have been unable to accurately reproduce melting curves and other temperature dependent behavior . The problems of inaccurate prediction of intermediate folded states and poor reproduction of melting curves arises from the overestimation of the steepness of the potential energy basins for protein‐protein interactions .…”

Review of the fundamental theories behind small angle X-ray scattering, molecular dynamics simulations, and relevant integrated application

“…Ferrara and Caflisch utilized MD simulation to study the reversible folding and free energy surface of two designed 20-residue sequences called beta3s (TWIQNGSTKWYQNGSTKIYT) and D PG (Ace-VFITSDPGKTYTEVDPG-Orn- KILQ-NH). Both of these sequences have a three-stranded antiparallel β -sheet topology ( 44 , 84 ). The beta3s have been examined previously by Nuclear Overhauser enhancement spectroscopy and chemical shift data, both of which showed that at 10°C, beta3s populates a single structured form-the three-stranded antiparallel β -sheet conformation with turns at Gly6-Ser7 and Gly14-Ser15 ( 44 , 85 ).…”

“…They provide an opportunity to study the physical characteristics of systems that are not easily examined in the laboratory ( 43 ). For example, there is active research aimed toward enhancing the MD algorithms, so they may simulate protein folding and unfolding ( 44 – 48 ). In addition to biological applications, MD simulations have been used to study the physical characteristics of non-biological nanoparticles ( 49 ).…”

Natural Food Colorants and Preservatives: A Review, a Demand, and a Challenge

“…Due to the complexity of biological and nonbiological systems, MD simulations have come under great interest for their ability to predict and verify experimental results, providing an opportunity to study the physical characteristics of systems that are not easily examined in the laboratory. Research aimed at improving MD algorithms so that they can simulate the folding and unfolding of proteins is one example of the study of these features. , In addition to biological applications, MD simulations have been used to study the physical characteristics of nonbiological nanoparticles . Comparisons of simulation and experimental data serve to test the accuracy of the calculated results and provide criteria for improving the methodology .…”