A fast and high-quality charge model for the next generation general AMBER force field

Abstract

The General AMBER Force Field (GAFF) has been broadly used by researchers all over the world to perform in silico simulations and modelings on diverse scientific topics, especially in the field of computer-aided drug design whose primary task is to accurately predict the affinity and selectivity of receptor-ligand binding. The atomic partial charges in GAFF and the second generation of GAFF (GAFF2) were originally developed with the quantum mechanics derived restrained electrostatic potential charge, but in practice, users usually adopt an efficient charge method, Austin Model 1-bond charge corrections (AM1-BCC), based on which, without expensive ab initio calculations, the atomic charges could be efficiently and conveniently obtained with the ANTECHAMBER module implemented in the AMBER software package. In this work, we developed a new set of BCC parameters specifically for GAFF2 using 442 neutral organic solutes covering diverse functional groups in aqueous solution. Compared to the original BCC parameter set, the new parameter set significantly reduced the mean unsigned error (MUE) of hydration free energies from 1.03 kcal/mol to 0.37 kcal/mol. More excitingly, this new AM1-BCC model also showed excellent performance in the solvation free energy (SFE) calculation on diverse solutes in various organic solvents across a range of different dielectric constants. In this large-scale test with totally 895 neutral organic solventsolute systems, the new parameter set led to accurate SFE predictions with the MUE and the root-mean-square-error of 0.51 kcal/mol and 0.65 kcal/mol, respectively. This newly developed charge model, ABCG2, paved a promising path for the next generation GAFF development.

Pathways and Mechanism of Caffeine Binding to Human Adenosine A2A Receptor

“…All chain termini were capped with neutral patches (acetyl and methylamide). The system was solvated in 0.15 M NaCl solution at temperature 310 K. The AMBER FF19SB ( Tian et al, 2019 ) parameter set was used for the receptor, LIPID17 (Gould et al, in preparation) for the POPC lipids, TIP3P ( Jorgensen et al, 1983 ) for water, and GAFF2 ( Wang et al, 2004 ; He et al, 2020 ) for CFF. The output files from CHARMM-GUI were used to perform GaMD simulations with AMBER 20 ( Case et al, 2020 ).…”

Mechanistic analysis of light-driven overcrowded alkene-based molecular motors by multiscale molecular simulations

“…No changes were considered to the functional form of the force field, the multiplicities and phases of torsional terms, and the partial atomic charges. Initial force field parameters were taken from general Amber force field (GAFF) version 2.1 [43,44] implemented in AmberTools18 [45], with AM1/BCC partial charges [46]. A subtlety of atom type selection for the motors is discussed in the Appendix C. For the dichloromethane solvent at room temperature and pressure, the GAFF2 parameters gave a density of 1.25 g cm −3 , in good agreement with the experimental value of 1.33 g cm −3 [47], so the GAFF2 parameters were used as is for the solvent.…”

Robust, Efficient and Automated Methods for Accurate Prediction of Protein-Ligand Binding Affinities in AMBER Drug Discovery Boost

“…The relative binding free energy simulations of the 1h1r to 1h1q were performed with the pmemd.cuda module of AMBER20. 19,21,22 The ligand was modeled using the GAFF2 force field, 125 and the condensed phase environment was explicitly modeled with TIP4P Ewald 126 waters. The whole ligands are defined as the transforming regions (TC+TS) while the phenyl ring is defined as the TS region.…”