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
Revealing the favorable dissociation pathway of type II kinase inhibitors via enhanced sampling simulations and two-end-state calculations
Huiyong Sun,Huiyong Sun,Sheng Tian,Shunye Zhou,Youyong Li,Dan Li,Lei Xu,Mingyun Shen,Peichen Pan,Tingjun Hou,Tingjun Hou +10 more
TL;DR: Interestingly, the MM/GBSA approach yielded similar PMF profiles compared with those based on US, a much time consuming approach, indicating that for a general study, such as detecting the important transition state of a ligand binding/unbinding process, MM/ GBSA may be a feasible choice.
Journal ArticleDOI
Copper−1,10-Phenanthroline Complexes Binding to DNA: Structural Predictions from Molecular Simulations
Arturo Robertazzi,Attilio Vittorio Vargiu,Alessandra Magistrato,Paolo Ruggerone,Paolo Carloni,Paul de Hoog,Jan Reedijk +6 more
TL;DR: It was found that a combination of factors including planarity, van der Waals interactions with DNA, and structural complementarities may be the key for the cleavage efficiency of these copper complexes.
Journal ArticleDOI
A water-swap reaction coordinate for the calculation of absolute protein–ligand binding free energies
TL;DR: The development of a new method that allows for the absolute binding free energy of a protein-ligand complex to be calculated from first principles, using a single simulation is presented, and the potential of mean force along the water-swap coordinate can be improved by calibrating the soft-core Coulomb and Lennard-Jones parameters used for the dual topology calculation.
Journal ArticleDOI
Less is more – multiscale modelling of self-assembling multivalency and its impact on DNA binding and gene delivery
TL;DR: The multiscale modelling of spermine-functionalised dendron designed to bind DNA and deliver it into cells provides an insight into the mode of self-assembly of the dendrons, in particular aggregate charge density and shape, and hence suggests explanations for some of the unexpected experimental observations.
Journal ArticleDOI
The Important Role of Halogen Bond in Substrate Selectivity of Enzymatic Catalysis.
TL;DR: By engineering the halogen interaction, the substrate selectivity of the enzyme changed, with the implication that halogen bond plays an important role in biosynthesis and should be used as an efficient and reliable tool in enzymatic drug synthesis.
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.