Biomolecular Simulations with the Three-Dimensional Reference Interaction Site Model with the Kovalenko-Hirata Closure Molecular Solvation Theory

Abstract

The statistical mechanics-based 3-dimensional reference interaction site model with the Kovalenko-Hirata closure (3D-RISM-KH) molecular solvation theory has proven to be an essential part of a multiscale modeling framework, covering a vast region of molecular simulation techniques. The successful application ranges from the small molecule solvation energy to the bulk phase behavior of polymers, macromolecules, etc. The 3D-RISM-KH successfully predicts and explains the molecular mechanisms of self-assembly and aggregation of proteins and peptides related to neurodegeneration, protein-ligand binding, and structure-function related solvation properties. Upon coupling the 3D-RISM-KH theory with a novel multiple time-step molecular dynamic (MD) of the solute biomolecule stabilized by the optimized isokinetic Nosé–Hoover chain thermostat driven by effective solvation forces obtained from 3D-RISM-KH and extrapolated forward by generalized solvation force extrapolation (GSFE), gigantic outer time-steps up to picoseconds to accurately calculate equilibrium properties were obtained in this new quasidynamics protocol. The multiscale OIN/GSFE/3D-RISM-KH algorithm was implemented in the Amber package and well documented for fully flexible model of alanine dipeptide, miniprotein 1L2Y, and protein G in aqueous solution, with a solvent sampling rate ~150 times faster than a standard MD simulation in explicit water. Further acceleration in computation can be achieved by modifying the extent of solvation layers considered in the calculation, as well as by modifying existing closure relations. This enhanced simulation technique has proven applications in protein-ligand binding energy calculations, ligand/solvent binding site prediction, molecular solvation energy calculations, etc. Applications of the RISM-KH theory in molecular simulation are discussed in this work.

Accurate Prediction of Hydration Sites of Proteins Using Energy Model With Atom Embedding

“…The distribution function has been used for hydration-site analysis of biomolecules ( Yoshidome et al, 2020 ), and also has been utilized as an intermediate to yield explicit hydration sites by the combining use of water-placement algorithms such as Placevent ( Sindhikara et al, 2012 ), which iteratively finds maximum points of the distribution function for atom insertion, and GAsol ( Fusani et al, 2018 ), a genetic algorithm that decides the occupancy of selected potential hydration sites. The quality of 3D-RISM results depends on the force field parameters used in its calculations, thus it requires careful parameter choices before being put in predictive purposes for specific systems ( Roy and Kovalenko, 2021 ). Masters et al (2018) studied the combination of WATsite and 3D-RISM with GAsol and claimed a better prediction by the joint model.…”

The Physical Chemistry and Chemical Physics (PCCP) Section of the International Journal of Molecular Sciences in Its Publications: The First 300 Thematic Articles in the First 3 Years

“…In conclusion of Thematic Area 5, it is worth mentioning review articles [ 187 , 188 , 189 ], which stand apart from other articles, since they are no longer devoted to specific organic or inorganic compounds, but general problems related to the molecular modeling of the structures of chemical compounds. In particular, Ref.…”

Multiscale Methods Framework with the 3D-RISM-KH Molecular Solvation Theory for Supramolecular Structures, Nanomaterials, and Biomolecules: Where Are We Going?

“…An extensive search of the available literature clearly indicates a clear classification of the possible schemes in handing (bio)chemical processes in solution, either by using continuum solvation models, or the so-called cluster continuum models and quasi-chemical models, all with system size limitations [2][3][4][5][6][7][8][9][10]. The other class of methods based on statistical mechanics, viz., the reference interaction site model (RISM), has been gaining popularity in addressing molecular systems in liquid media due to its reasonable accuracy, speed of calculation, and extendibility over the entire scale of the molecular size and time scales [11,12]. The molecular solvation theory with integral equation formalism is based on the modified Ornstein-Zernike (OZ) theory for the dimensional reduction of molecular liquids [13].…”