The Ion-Dipole Correction of the 3DRISM Solvation Model to Accurately Compute Water Distributions around Negatively Charged Biomolecules

Abstract

The 3D reference interaction site model (3DRISM) provides an efficient grid-based solvation model to compute the structural and thermodynamic properties of biomolecules in aqueous solutions. However, it remains challenging for existing 3DRISM methods to correctly predict water distributions around negatively charged solute molecules. In this paper, we first show that this challenge is mainly due to the orientation of water molecules in the first solvation shell of the negatively charged solute molecules. To properly consider this orientational preference, position-dependent two-body intramolecular correlations of solvent need to be included in the 3DRISM theory, but direct evaluations of these position-dependent two-body intramolecular correlations remain numerically intractable. To address this challenge, we introduce the Ion-Dipole Correction (IDC) to the 3DRISM theory, in which we incorporate the orientation preference of water molecules via an additional solute–solvent interaction term (i.e., the ion-dipole interaction) while keeping the formulism of the 3DRISM equation unchanged. We prove that this newly introduced IDC term is equivalent to an effective direct correlation function which can effectively consider the orientation effect that arises from position dependent two-body correlations. We first quantitatively validate our 3DRISM-IDC theory combined with the PSE3 closure on Cl–, [ClO]− (a two-site anion), and [NO2]− (a three-site anion). For all three anions, we show that our 3DRISM-IDC theory significantly outperforms the 3DRISM theory in accurately predicting the solvation structures in comparison to MD simulations, including RDFs and 3D water distributions. Furthermore, we have also demonstrated that the 3DRISM-IDC can improve the accuracy of hydration free-energy calculation for Cl–. We further demonstrate that our 3DRISM-IDC theory yields significant improvements over the 3DRISM theory when applied to compute the solvation structures for various negatively charged solute molecules, including adenosine triphosphate (ATP), a short peptide containing 19 residues, a DNA hairpin containing 24 nucleotides, and a riboswitch RNA molecule with 77 nucleotides. We expect that our 3DRISM-IDC-PSE3 solvation model holds great promise to be widely applied to study solvation properties for nucleic acids and other biomolecules containing negatively charged functional groups.

EPISOL: A Software Package with Expanded Functions to Perform 3D-RISM Calculations for the Solvation of Chemical and Biological Molecules

“…We have recently developed the IDC theory to address this issue by considering the position dependence of solvent intramolecular correlation. In IDC, we have introduced a correction to the solute-solvent interactions to consider the energetic effect induced by the position dependence of the solvent intramolecular correlations 63 . The IDC is implemented in EPISOL via a modification of LJ interactions, and 3D-RISM-IDC is the same as 3D-RISM except that the LJ interactions are calculated with modified LJ parameters.…”

“…For example, a strong orientation preference is observed with explicit-solvent MD simulations for water molecules surrounding anions 63 . Recently, the ion-dipole correction (IDC) has been introduced to 3D-RISM to address this issue 63 . 1D-RISM is often used to generate the solvent-solvent correlations like in AMBER-RISM 49 .…”

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

“…To address this issue, the hydrophobicity‐induced density inhomogeneity (HI) theory has been developed by introducing an additional HI equation to consider the slow‐varying density at the hydrophobic surface. Furthermore, 3D‐RISM does not accurately predict water distributions around negatively charged or electron‐rich solute groups 63 . This is because 3D‐RISM assumes that the conformations of solvent molecules are directionless, which is only correct for a bulk solvent, but is inaccurate when water molecules are near negatively charged solute groups.…”

“…This is because 3D‐RISM assumes that the conformations of solvent molecules are directionless, which is only correct for a bulk solvent, but is inaccurate when water molecules are near negatively charged solute groups. For example, a strong orientation preference is observed with explicit‐solvent MD simulations for water molecules surrounding anions 63 . Recently, the ion‐dipole correction (IDC) has been introduced to 3D‐RISM to address this issue 63 …”

Biomolecular Electrostatic Phenomena: An Evergreen Field

“…16 Approximately one-third of the contributions to this virtual special issue concerned methodological aspects, considered from many different points of view. Improvements to continuum models were discussed regarding a better prediction of water molecule distribution around negatively charged solutes, 17 and introducing better analytical estimates of the interaction energy of dielectric particles in a solvent obeying the linearized Poisson−Boltzmann equation. 18 The same solvent model was assumed in the development of an improved version of the TABI-PB solver.…”