Journal ArticleDOI
Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models
Peter A. Kollman,Irina Massova,Carolina M. Reyes,Bernd Kuhn,Shuanghong Huo,Lillian T. Chong,Matthew Lee,Tai-Sung Lee,Yong Duan,Wei Wang,Oreola Donini,Piotr Cieplak,Jaysharee Srinivasan,David A. Case,Thomas E. Cheatham +14 more
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TLDR
A historical perspective on the application of molecular dynamics to biological macromolecules is presented and recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed for the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories.Abstract:
A historical perspective on the application of molecular dynamics (MD) to biological macromolecules is presented. Recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed us to reach the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories. We illustrate such applications on nucleic acid duplexes, RNA hairpins, protein folding trajectories, and protein−ligand, protein−protein, and protein−nucleic acid interactions.read more
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The Amber biomolecular simulation programs
David A. Case,Thomas E. Cheatham,Tom Darden,Holger Gohlke,Ray Luo,Kenneth M. Merz,Alexey V. Onufriev,Carlos Simmerling,Bing Wang,Robert J. Woods +9 more
TL;DR: The development, current features, and some directions for future development of the Amber package of computer programs, which contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates.
Journal ArticleDOI
g_mmpbsa--a GROMACS tool for high-throughput MM-PBSA calculations.
TL;DR: A new tool, g_mmpbsa, which implements the MM-PBSA approach using subroutines written in-house or sourced from the GROMACS and APBS packages is described, and the calculated interaction energy of 37 structurally diverse HIV-1 protease inhibitor complexes is compared.
Journal ArticleDOI
Docking and scoring in virtual screening for drug discovery: methods and applications.
TL;DR: Key concepts and specific features of small-molecule–protein docking methods are reviewed, selected applications are highlighted and recent advances that aim to address the acknowledged limitations of established approaches are discussed.
Journal ArticleDOI
The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities
Samuel Genheden,Ulf Ryde +1 more
TL;DR: The authors review the use of MM/PBSA and MM/GBSA methods to calculate ligand-binding affinities, with an emphasis on calibration, testing and validation, as well as attempts to improve the methods, rather than on specific applications.
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Exploring protein native states and large-scale conformational changes with a modified generalized born model.
TL;DR: A popular analytical Generalized Born (GB) solvation model is modified to improve its accuracy in calculating the solvent polarization part of free energy changes in large‐scale conformational transitions, such as protein folding.
References
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Journal ArticleDOI
Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems
TL;DR: An N⋅log(N) method for evaluating electrostatic energies and forces of large periodic systems is presented based on interpolation of the reciprocal space Ewald sums and evaluation of the resulting convolutions using fast Fourier transforms.
Book
Computer Simulation of Liquids
Michael P. Allen,D. J. Tildesley +1 more
TL;DR: In this paper, the gear predictor -corrector is used to calculate forces and torques in a non-equilibrium molecular dynamics simulation using Monte Carlo methods. But it is not suitable for the gear prediction problem.
Journal ArticleDOI
A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules
Wendy D. Cornell,Piotr Cieplak,Piotr Cieplak,Christopher I. Bayly,Christopher I. Bayly,Ian R. Gould,Ian R. Gould,Kenneth M. Merz,Kenneth M. Merz,David M. Ferguson,David M. Ferguson,David C. Spellmeyer,David C. Spellmeyer,Thomas R. Fox,James W. Caldwell,Peter A. Kollman +15 more
TL;DR: Weiner et al. as mentioned in this paper derived a new molecular mechanical force field for simulating the structures, conformational energies, and interaction energies of proteins, nucleic acids, and many related organic molecules in condensed phases.
Journal ArticleDOI
Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models
TL;DR: In this paper, a method and parametrization scheme which allow fast and accurate calculations of hydration free energies is described, where the solute is treated as a polarizable cavity of a shape defined by the molecular surface, containing point charges at the location of atomic nuclei.
Journal ArticleDOI
Free energy calculations : applications to chemical and biochemical phenomena
TL;DR: In this article, the authors review the applications of free energy calculations employing molecular dynamics or Monte Carlo methods to a variety of chemical and biochemical phenomena, including molecular solvation, molecular association, macromolecular stability, and enzyme catalysis.