Journal ArticleDOI
Development and testing of a general amber force field.
Reads0
Chats0
TLDR
A general Amber force field for organic molecules is described, designed to be compatible with existing Amber force fields for proteins and nucleic acids, and has parameters for most organic and pharmaceutical molecules that are composed of H, C, N, O, S, P, and halogens.Abstract:
We describe here a general Amber force field (GAFF) for organic molecules. GAFF is designed to be compatible with existing Amber force fields for proteins and nucleic acids, and has parameters for most organic and pharmaceutical molecules that are composed of H, C, N, O, S, P, and halogens. It uses a simple functional form and a limited number of atom types, but incorporates both empirical and heuristic models to estimate force constants and partial atomic charges. The performance of GAFF in test cases is encouraging. In test I, 74 crystallographic structures were compared to GAFF minimized structures, with a root-mean-square displacement of 0.26 A, which is comparable to that of the Tripos 5.2 force field (0.25 A) and better than those of MMFF 94 and CHARMm (0.47 and 0.44 A, respectively). In test II, gas phase minimizations were performed on 22 nucleic acid base pairs, and the minimized structures and intermolecular energies were compared to MP2/6-31G* results. The RMS of displacements and relative energies were 0.25 A and 1.2 kcal/mol, respectively. These data are comparable to results from Parm99/RESP (0.16 A and 1.18 kcal/mol, respectively), which were parameterized to these base pairs. Test III looked at the relative energies of 71 conformational pairs that were used in development of the Parm99 force field. The RMS error in relative energies (compared to experiment) is about 0.5 kcal/mol. GAFF can be applied to wide range of molecules in an automatic fashion, making it suitable for rational drug design and database searching.read more
Citations
More filters
Journal ArticleDOI
Glutathione transferase: new model for glutathione activation.
TL;DR: A mechanism of GSH activation in which a water molecule, acting as a bridge, is able to assist in the transfer of the proton from the GSH thiol group to the G SHS glutamyl alpha-carboxylate group, after an initial GSH conformational rearrangement is proposed.
Journal ArticleDOI
Applications of Molecular Dynamics Simulation in Structure Prediction of Peptides and Proteins.
TL;DR: It is shown that all-atom MD can predict structures of cyclic peptides and other peptide foldamers with accuracy similar to experiments, and some notable successes in reproducing experimental 3D structures of small proteins through MD simulations were summarized.
Journal ArticleDOI
Calculation of Host-Guest Binding Affinities Using a Quantum-Mechanical Energy Model.
TL;DR: The present study reports the first mining minima (M2) binding affinity calculations based on a quantum mechanical energy model, rather than an empirical force field, to apply to 29 host-guest systems with a wide range of measured binding affinities.
Journal ArticleDOI
Predicting Residence Time and Drug Unbinding Pathway through Scaled Molecular Dynamics.
Doris A. Schuetz,Mattia Bernetti,Martina Bertazzo,Martina Bertazzo,Djordje Musil,Hans-Michael Eggenweiler,Maurizio Recanatini,Matteo Masetti,Gerhard F. Ecker,Andrea Cavalli,Andrea Cavalli +10 more
TL;DR: Scaled molecular dynamics simulations are challenged to assess the off-rates for a series of structurally diverse inhibitors of the heat shock protein 90 covering 3 orders of magnitude in their experimental residence times to lead to better understanding of the mechanistic aspects related to the observed kinetic behavior.
Journal ArticleDOI
Extending the horizon: towards the efficient modeling of large biomolecular complexes in atomic detail
TL;DR: The work described herein will lead to new, efficient modeling tools that will allow the simulation of longer timescales and larger system sizes in order to meet current and future challenges by the experimental community.
References
More filters
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
A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model
TL;DR: In this paper, the authors present an approach to generate electrostatic potential (ESP) derived charges for molecules, which optimally reproduce the intermolecular interaction properties of molecules with a simple two-body additive potential, provided that a suitably accurate level of quantum mechanical calculation is used to derive the ESP around the molecule.
Journal ArticleDOI
Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94
TL;DR: The first published version of the Merck molecular force field (MMFF) is MMFF94 as mentioned in this paper, which is based on the OPLS force field and has been applied to condensed-phase processes.
Journal ArticleDOI
A new force field for molecular mechanical simulation of nucleic acids and proteins
S. J. Weiner,Peter A. Kollman,David A. Case,U. C. Singh,Caterina Ghio,Giuliano Alagona,Salvatore Profeta,Paul K. Weiner +7 more
TL;DR: In this paper, a force field for simulation of nucleic acids and proteins is presented, which is based on the ECEPP, UNECEPP, and EPEN energy refinement software.
Journal ArticleDOI
How Well Does a Restrained Electrostatic Potential (RESP) Model Perform in Calculating Conformational Energies of Organic and Biological Molecules
TL;DR: In this paper, the authors present conformational energies for a molecular mechanical model (Parm99) developed for organic and biological molecules using the restrained electrostatic potential (RESP) approach to derive the partial charges.