EPISOL: A software package with expanded functions to perform 3D‐RISM calculations for the solvation of chemical and biological molecules

Abstract

Integral equation theory (IET) provides an effective solvation model for chemical and biological systems that balances computational efficiency and accuracy. We present a new software package, the expanded package for IET-based solvation (EPISOL), that performs 3D-reference interaction site model (3D-RISM) calculations to obtain the solvation structure and free energies of solute molecules in different solvents. In EPISOL, we have implemented 22 different closures, multiple free energy functionals, and new variations of 3D-RISM theory, including the recent hydrophobicity-induced density inhomogeneity (HI) theory for hydrophobic solutes and ion-dipole correction (IDC) theory for negatively charged solutes. To speed up the convergence and enhance the stability of the self-consistent iterations, we have introduced several numerical schemes in EPISOL, including a newly developed dynamic mixing approach. We show that these schemes have significantly reduced the failure rate of 3D-RISM calculations compared to AMBER-RISM software. EPISOL consists of both a user-friendly graphic interface and a kernel library that allows users to call its routines and adapt them to other programs. EPISOL is compatible with the force-field and coordinate files from both AMBER and GROMACS simulation packages. Moreover, EPISOL is equipped with an internal memory control to efficiently manage the use of physical memory, making it suitable for performing calculations on large biomolecules. We demonstrate that EPI-SOL can efficiently and accurately calculate solvation density distributions around various solute molecules (including a protein chaperone consisting of 120,715 atoms) and obtain solvent free energy for a wide range of organic compounds. We expect that EPISOL can be widely applied as a solvation model for chemical and biological systems.

RISMiCal: A software package to perform fastRISM/3D‐RISMcalculations

“…Due to the high computational cost of the 3D-RISM calculations, several convergence acceleration methods have been proposed to reduce the number of convergence times: the Picard iteration with dynamic relaxation (the dynamic relaxation method), 20 the modified procedure of the direct inversion in the iterative subspace (MDIIS), 104 the multigrid algorithm, 105 the modified Anderson method, 95 and the static mixing approach. 87 Among these, the MDIIS is the most widely used.…”

“…The RISM/3D-RISM program in one of the most representative programs, AmberTools, is useful for analyzing the biomolecular systems solvation in combination with the Amber MD simulation package developed by Luchko et al 83 EPISOL, developed by Cao et al, 87 is another program for the application of 3D-RISM for a biomolecular system. For a supercomputer system, the RISM for HPC was developed by Wilson, Kobryn, and Sergey and applied to large biomolecular systems.…”

The Three-Dimensional Reference Interaction Site Model Approach as a Promising Tool for Studying Hydrated Viruses and Their Complexes with Ligands

“…Moreover, although MD simulations can study the behavior of biomolecules in full atomic detail and at very fine temporal resolution, in the case of viruses, they cannot reproduce all the details of the binding of the virus with the host cell due to high computational costs and the need for a large conformational space [62]. To date, the 3D-RISM method has been implemented in a number of software packages in the field of computational chemistry and materials, such as ADF [63], AMBER [64], AutoDock [65], EPISOL [66], MOE [67], NWChem [68,69], Quantum Espresso [70], etc., and is thus available to researchers.…”