Comparison of multiple Amber force fields and development of improved protein backbone parameters.
Viktor Hornak,Robert Abel,Asim Okur,Bentley Strockbine,Adrian E. Roitberg,Carlos Simmerling,Carlos Simmerling +6 more
TLDR
An effort to improve the φ/ψ dihedral terms in the ff99 energy function achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data.Abstract:
The ff94 force field that is commonly associated with the Amber simulation package is one of the most widely used parameter sets for biomolecular simulation. After a decade of extensive use and testing, limitations in this force field, such as over-stabilization of alpha-helices, were reported by us and other researchers. This led to a number of attempts to improve these parameters, resulting in a variety of "Amber" force fields and significant difficulty in determining which should be used for a particular application. We show that several of these continue to suffer from inadequate balance between different secondary structure elements. In addition, the approach used in most of these studies neglected to account for the existence in Amber of two sets of backbone phi/psi dihedral terms. This led to parameter sets that provide unreasonable conformational preferences for glycine. We report here an effort to improve the phi/psi dihedral terms in the ff99 energy function. Dihedral term parameters are based on fitting the energies of multiple conformations of glycine and alanine tetrapeptides from high level ab initio quantum mechanical calculations. The new parameters for backbone dihedrals replace those in the existing ff99 force field. This parameter set, which we denote ff99SB, achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data. It also accomplishes improved agreement with published experimental data for conformational preferences of short alanine peptides and better accord with experimental NMR relaxation data of test protein systems.read more
Citations
More filters
Journal ArticleDOI
Highly accurate protein structure prediction with AlphaFold
John M. Jumper,Richard O. Evans,Alexander Pritzel,Tim Green,Michael Figurnov,Olaf Ronneberger,Kathryn Tunyasuvunakool,Russell Bates,Augustin Žídek,Anna Potapenko,Alex Bridgland,Clemens Meyer,Simon A. A. Kohl,Andrew J. Ballard,Andrew Cowie,Bernardino Romera-Paredes,Stanislav Nikolov,R. D. Jain,Jonas Adler,Trevor Back,Stig Petersen,David Reiman,Ellen Clancy,Michal Zielinski,Martin Steinegger,Michalina Pacholska,Tamas Berghammer,Sebastian Bodenstein,David L. Silver,Oriol Vinyals,Andrew W. Senior,Koray Kavukcuoglu,Pushmeet Kohli,Demis Hassabis +33 more
TL;DR: For example, AlphaFold as mentioned in this paper predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture. But the accuracy is limited by the fact that no homologous structure is available.
Journal ArticleDOI
ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB
James Maier,Carmenza Martinez,Koushik Kasavajhala,Lauren Wickstrom,Kevin Hauser,Carlos Simmerling +5 more
TL;DR: Together, these backbone and side chain modifications (hereafter called ff14SB) not only better reproduced their benchmarks, but also improved secondary structure content in small peptides and reproduction of NMR χ1 scalar coupling measurements for proteins in solution.
Journal ArticleDOI
Improved side‐chain torsion potentials for the Amber ff99SB protein force field
Kresten Lindorff-Larsen,Stefano Piana,Kim Palmo,Paul Maragakis,John L. Klepeis,Ron O. Dror,David E. Shaw,David E. Shaw +7 more
TL;DR: A new force field, which is termed Amber ff99SB‐ILDN, exhibits considerably better agreement with the NMR data and is validated against a large set of experimental NMR measurements that directly probe side‐chain conformations.
Journal ArticleDOI
Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles.
Robert B. Best,Xiao Zhu,Jihyun Shim,Pedro E. M. Lopes,Jeetain Mittal,Michael Feig,Alexander D. MacKerell +6 more
TL;DR: The results indicate that the revised CHARMM 36 parameters represent an improved model for the modeling and simulation studies of proteins, including studies of protein folding, assembly and functionally relevant conformational changes.
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.
References
More filters
Journal ArticleDOI
Comparison of simple potential functions for simulating liquid water
TL;DR: In this article, the authors compared the Bernal Fowler (BF), SPC, ST2, TIPS2, TIP3P, and TIP4P potential functions for liquid water in the NPT ensemble at 25°C and 1 atm.
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.
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
Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids
TL;DR: In this article, the parametrization and testing of the OPLS all-atom force field for organic molecules and peptides are described, and the parameters for both torsional and non-bonded energy properties have been derived, while the bond stretching and angle bending parameters have been adopted mostly from the AMBER force field.
Journal ArticleDOI
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.