Recent advances in implicit solvent-based methods for biomolecular simulations

Abstract

Implicit solvent-based methods play an increasingly important role in molecular modeling of biomolecular structure and dynamics. Recent methodological developments have mainly focused on the extension of the generalized Born (GB) formalism for variable dielectric environments and accurate treatment of nonpolar solvation. Extensive efforts in parameterization of GB models and implicit solvent force fields have enabled ab initio simulation of protein folding to native or near-native structures. Another exciting area that has benefited from the advances in implicit solvent models is the development of constant pH molecular dynamics methods, which have recently been applied to the calculations of protein pK(a) values and the studies of pH-dependent peptide and protein folding.

Electrostatics in Proteins and Protein–Ligand Complexes

“…With improvements in recent years, current GBSA models are capable of achieving the similar level of accuracy as numerical PBSA methods [42,52]. Their high computational efficiency makes them suitable for drug-design applications and different versions of GBSA models are implemented now in many liganddocking programs [53][54][55][56].…”

An improved coarse-grained model of solvation and the hydrophobic effect

“…Hummer et al introduced the idea of characterizing this distribution in the context of solvation theory, 34 and the utility of this function has been demonstrated subsequently. 33,[35][36][37] The GBSA model, 10,11 widely used in biological settings, captures the effect of electrostatics with reasonable accuracy, but its treatment of the hydrophobic effect is less adequate, 20,[38][39][40] for the reasons discussed above. Interesting examples of solutes for which hydrophobicity is essential, and for which GBSA is unsuitable, include large classes of proteins, such as those involved in transmembrane protein recognition and insertion, 41 and versatile chaperones.…”

Development of constant-pH simulation methods in implicit solvent and applications in biomolecular systems

“…Different aspects of available computational methods to study acid-base processes in biomolecules have been reviewed in the literature (Mongan and Case 2005;Chen et al 2008Chen et al , 2014Wallace and Shen 2009;Alexov et al 2011;Kim and McCammon 2016), evidencing their increasingly important role in biophysics, biochemistry, and biotechnological processes. Most of the reviews concentrated their discussions on atomistic level constant-pH (CpH) molecular dynamics (MD) techniques.…”