Journal ArticleDOI
Development and testing of a general amber force field.
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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
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Journal ArticleDOI
Molecular mechanical study of halogen bonding in drug discovery
TL;DR: This research is the first reported molecular mechanical study of halogen bonding, the positive region centered on the halogen atom was represented by an extra‐point (EP) of charge, which resulted in an improvement in the accuracy of the electrostatic‐potential derived charges.
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Computational identification of a transiently open L1/S3 pocket for reactivation of mutant p53
Christopher D. Wassman,Roberta Baronio,Özlem Demir,Özlem Demir,Brad D. Wallentine,Chiung-Kuang Chen,Linda V. Hall,Faezeh Salehi,Dawei Lin,Benjamin P. Chung,G. Wesley Hatfield,A. Richard Chamberlin,Hartmut Luecke,Richard H. Lathrop,Peter K. Kaiser,Rommie E. Amaro +15 more
TL;DR: In this paper, a transiently open binding pocket between loop L1 and sheet S3 of the p53 core domain was identified as a target for pharmaceutical reactivation of p53 mutants.
Journal ArticleDOI
GAFFlipid: a General Amber Force Field for the accurate molecular dynamics simulation of phospholipid
TL;DR: In this paper, the GAFF Lennard-Jones parameters for the simulation of acyl chains are corrected to allow the accurate and stable simulation of pure lipid bilayers, which is intended for combination with the new AMBER Lipid11 modular force field as part of ongoing attempts to create a modular phospholipid AMBER force field allowing tensionless NPT simulations of complex lipid bilayer.
Journal ArticleDOI
Modeling Amorphous Microporous Polymers for CO2 Capture and Separations.
TL;DR: The review provides general guidelines and a comprehensive update of the recent literature to promote the acceleration of the discovery and screening of amorphous microporous polymers for CO2 capture and separation processes.
Journal ArticleDOI
Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals)
Matthias Schiedel,Daniel Herp,Sören Hammelmann,Sören Swyter,Attila Lehotzky,Dina Robaa,Judit Oláh,Judit Ovádi,Wolfgang Sippl,Manfred Jung +9 more
TL;DR: This SirReal-based PROTAC is the first example of a probe that is able to chemically induce the degradation of an epigenetic eraser protein and can be readily adapted to alkynylated ligands of other targets.
References
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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.