Accurate Absorption Energy Calculations in Solution Using the Reference Interaction Site Model Self-Consistent Field Including the Constrained Spatial Electron Density Distribution

The solvation effect is an important factor determining the properties of molecules in solution. The reference interaction site model (RISM) is a powerful method to treat the solvation effect with pair-correlation functions, such as a radial distribution function. This study developed a hybrid method between quantum mechanics and RISM using the spatial electron density distributions on each atomic site (RISM-SCF-cSED). Sophisticated quantum mechanical approaches can be used to consider the solvation effect because the computational cost of RISM-SCF-cSED is reasonable. In this study, the absorption energies of 5-(dimethylamino)-2,4-pentadienal in various solutions were calculated using RISM-SCF-cSED. The experimental data were well reproduced with an average errors of ∼0.06 eV, using multi-reference perturbation theory.

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

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.

Early stages of aggregation in fluid mixtures of dimers and spheres: a theoretical and simulation study

We use Monte Carlo simulation and the Reference Interaction Site Model (RISM) theory of molecular fluids to investigate a simple model of colloidal mixture consisting of dimers, made up of...