AGBNP: An analytic implicit solvent model suitable for molecular dynamics simulations and high‐resolution modeling

Abstract

We have developed an implicit solvent effective potential (AGBNP) that is suitable for molecular dynamics simulations and high-resolution modeling. It is based on a novel implementation of the pairwise descreening Generalized Born model for the electrostatic component and a new nonpolar hydration free energy estimator. The nonpolar term consists of an estimator for the solute-solvent van der Waals dispersion energy designed to mimic the continuum solvent solute-solvent van der Waals interaction energy, in addition to a surface area term corresponding to the work of cavity formation. AGBNP makes use of a new parameter-free algorithm to calculate the scaling coefficients used in the pairwise descreening scheme to take into account atomic overlaps. The same algorithm is also used to calculate atomic surface areas. We show that excellent agreement is achieved for the GB self-energies and surface areas in comparison to accurate, but much more expensive, numerical evaluations. The parameter-free approach used in AGBNP and the sensitivity of the AGBNP model with respect to large and small conformational changes makes the model suitable for high-resolution modeling of protein loops and receptor sites as well as high-resolution prediction of the structure and thermodynamics of protein-ligand complexes. We present illustrative results for these kinds of benchmarks. The model is fully analytical with first derivatives and is computationally efficient. It has been incorporated into the IMPACT molecular simulation program.

Poisson–Boltzmann model analysis of binding mRNA cap analogues to the translation initiation factor eIF4E

“…However we should add that some consistent coupling of non polar and polar solvation free energies in the context of computation of the binding free energies is desired and such work is in progress [50]. It is also useful to point to recent important improvements in modelling non polar contributions to free energy of binding, particularly a recognition of non polar attractive and repulsive contributions to free energy of binding which must be modelled separately [51,52,53].…”

Computational Methods for Biomolecular Electrostatics

“…Although SASA methods have enjoyed surprising success, they are also subject to several caveats, including widely varying choices of surface tension parameter (Chothia, 1974;Eisenberg and McLachlan, 1986;Sharp et al, 1991;Sitkoff et al, 1994a;Elcock et al, 2001) as well as inaccurate descriptions of the detailed aspects of nonpolar solvation energy (Gallicchio and Levy, 2004), peptide conformations (Su and Gallicchio, 2004), and protein nonpolar solvation forces (Wagoner and Baker, 2004). Some of these problems have been fixed by new models which include the small but important attractive van der Waals interactions between solvent and solute (Gallicchio et al, 2000;Gallicchio et al, 2002;Gallicchio and Levy, 2004;Wagoner and Baker, 2006) as well as repulsive solvent-accessible volume terms (Wagoner and Baker, 2006). III.B.2.…”

Prediction of Protein Loop Conformations Using the AGBNP Implicit Solvent Model and Torsion Angle Sampling

“…44 It is assumed in the distance-dependent dielectric model that the interaction energy between partial charges in a heterogeneous dielectric environment follows a simple Coulomb law. The Coulomb energy term is given by, (1) where r ij is the interatomic distance between atoms i and j, and ε is the dielectric constant.…”