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
Modulation of global low-frequency motions underlies allosteric regulation : demonstration in CRP/FNR family transcription factors.
Thomas L. Rodgers,Philip D. Townsend,David Burnell,Matthew L. Jones,Shane A. Richards,Tom McLeish,Ehmke Pohl,Mark R. Wilson,Martin J. Cann +8 more
TL;DR: Allostery in bacterial transcription factors arises from changes in global low-frequency protein dynamics and Amino acids that regulate low- frequency dynamics are identified and seen to be evolutionarily conserved.
Journal ArticleDOI
Integrated QM/polarizable MM/continuum approaches to model chiroptical properties of strongly interacting solute–solvent systems
TL;DR: In this paper, a recently developed integrated Quantum-Mechanical/Polarizable molecular mechanics (MM)/polarizable continuum model (PCM) method is discussed, which combines a fluctuating charge approach to the MM polarization with the PCM.
Journal ArticleDOI
Metformin is a novel suppressor for transforming growth factor (TGF)-β1
Han Xiao,Jianshu Zhang,Zhonghe Xu,Yenan Feng,Mingliang Zhang,Jianli Liu,Ruifei Chen,Jing Shen,Jimin Wu,Zhizhen Lu,Xiaohong Fang,Jingyuan Li,Youyi Zhang +12 more
TL;DR: The results indicate that metformin is a novel TGF-β suppressor with therapeutic potential for numerous diseases in which T GF-β1 hyperfunction is indicated.
Journal ArticleDOI
Delineating the conformational landscape of the adenosine A2A receptor during G protein coupling
Shuya Kate Huang,Aditya Pandey,Duy Phuoc Tran,Nicolas Villanueva,Akio Kitao,Roger K. Sunahara,Adnan Sljoka,R. Scott Prosser +7 more
TL;DR: In this paper, fluorine nuclear magnetic resonance spectroscopy (19F NMR) was used to delineate key functional states of the adenosine A2A receptor (A2AR) complexed with heterotrimeric G protein (Gαsβ1γ2).
Journal ArticleDOI
Aβ(39–42) Modulates Aβ Oligomerization but Not Fibril Formation
TL;DR: The results suggest that Aβ(39-42) inhibits Aβ-induced toxicity by a unique mechanism, modulating early assembly into nontoxic hetero-oligomers, without preventing fibril formation.
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.