Integrated Modeling Program, Applied Chemical Theory (IMPACT)

Abstract

We provide an overview of the IMPACT molecular mechanics program with an emphasis on recent developments and a description of its current functionality. With respect to core molecular mechanics technologies we include a status report for the fixed charge and polarizable force fields that can be used with the program and illustrate how the force fields, when used together with new atom typing and parameter assignment modules, have greatly expanded the coverage of organic compounds and medicinally relevant ligands. As we discuss in this review, explicit solvent simulations have been used to guide our design of implicit solvent models based on the generalized Born framework and a novel nonpolar estimator that have recently been incorporated into the program. With IMPACT it is possible to use several different advanced conformational sampling algorithms based on combining features of molecular dynamics and Monte Carlo simulations. The program includes two specialized molecular mechanics modules: Glide, a high-throughput docking program, and QSite, a mixed quantum mechanics/molecular mechanics module. These modules employ the IMPACT infrastructure as a starting point for the construction of the protein model and assignment of molecular mechanics parameters, but have then been developed to meet specialized objectives with respect to sampling and the energy function.

Structural factors affecting 13C NMR chemical shifts of cellulose: a computational study

“…Energy minimizations and molecular dynamics simulations were performed using the OPLS_2005 force field (Banks et al 2005) keeping the atomic positions of cellulose molecules fixed. 1000 steps of conjugate gradient minimization were performed before 10 ps molecular dynamics simulations at 298 K with a 1 fs time step in the NVT ensemble.…”

Synthesis, Structural Elucidation, and Biological Evaluation of NSC12, an Orally Available Fibroblast Growth Factor (FGF) Ligand Trap for the Treatment of FGF-Dependent Lung Tumors

“…The structures of compounds 9, 11, 12, and 13 were built with Maestro 9.7,24 and their geometries were optimized with OPLS2005 force field in combination with an implicit solvent model (water) using a convergence criterion for energy minimization of 0.05 kcal mol −1 Å −1 . 35 A model of FGF2 was built, by the Protein Preparation Wizard of Maestro 9.7, from the crystal coordinates of a ternary FGF2-FGFR1-heparin complex (PDB code 1fq9). In the final structure, the C and N termini were capped with a methylamino and an acetyl group, respectively; glutamate and aspartate residues were deprotonated, lysines and arginines were protonated, and histidines were in their neutral form.…”

Computational modelling of the binding of arachidonic acid to the human monooxygenase CYP2J2

“…Ionisation states were assigned by Epik [35] at physiological pH (7.0). Parameters were assigned using the OPLS2005 force field [36].…”