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
Importance of Dispersion and Electron Correlation in ab Initio Protein Folding
TL;DR: It is shown that the sum of the Hartree-Fock (HF) energy and force field (LJ6)-derived dispersion energy is well correlated with the energies obtained using second-order Møller-Plesset perturbation (MP2) theory.
Journal ArticleDOI
Molecular Basis of Filtering Carbapenems by Porins from β-Lactam-resistant Clinical Strains of Escherichia coli
Harsha Bajaj,Mariano Andrea Scorciapino,Lucile Moynié,Malcolm G. P. Page,James H. Naismith,Matteo Ceccarelli,Mathias Winterhalter +6 more
TL;DR: Investigation of four mutant OmpC proteins from four different clinical isolates of Escherichia coli obtained sequentially from a single patient during a course of antimicrobial chemotherapy finds that changes in the vector of the electric field in the mutated porin create an additional barrier by “trapping” the antibiotic in an unfavorable orientation in the constriction zone.
Journal ArticleDOI
Theoretical studies on the susceptibility of oseltamivir against variants of 2009 A/H1N1 influenza neuraminidase.
TL;DR: Molecular simulations show that N294S and H274Y, two popular drug-resistant mutations in different variants of NA, still cause significant resistance to oseltamivir, and the results will be useful for the rational design of NA inhibitors with high potency against drug- resistant A/H1N1 mutants.
Journal ArticleDOI
Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis
Patricia Santofimia-Castaño,Yi Xia,Wenjun Lan,Zhengwei Zhou,Can Huang,Ling Peng,Philippe Soubeyran,Adrián Velázquez-Campoy,Olga Abian,Bruno Rizzuti,José L. Neira,Juan L. Iovanna +11 more
TL;DR: A multidisciplinary approach was undertook to optimize TFP, based on the synergy of computer modeling, chemical synthesis, and a variety of biophysical, biochemical and biological evaluations, demonstrating the possibility of successful ligand-based drug design for such challenging targets.
Journal ArticleDOI
Experimental and computational determination of tRNA dynamics.
TL;DR: The effects of modified bases, ions, and proteins on tRNA structure and dynamics and the challenges of observing its motions over the cycle of translation are discussed.
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.