“Solvent hydrogen‐bond occlusion”: A new model of polar desolvation for biomolecular energetics

Abstract

Water engages in two important types of interactions near biomolecules: it forms ordered “cages” around exposed hydrophobic regions, and it participates in hydrogen bonds with surface polar groups. Both types of interaction are critical to biomolecular structure and function, but explicitly including an appropriate number of solvent molecules makes many applications computationally intractable. A number of implicit solvent models have been developed to address this problem, many of which treat these two solvation effects separately. Here we describe a new model to capture polar solvation effects, called SHO (“solvent hydrogen-bond occlusion”); our model aims to directly evaluate the energetic penalty associated with displacing discrete first-shell water molecules near each solute polar group. We have incorporated SHO into the Rosetta energy function, and find that scoring protein structures with SHO provides superior performance in loop modeling, virtual screening, and protein structure prediction benchmarks. These improvements stem from the fact that SHO accurately identifies and penalizes polar groups that do not participate in hydrogen bonds, either with solvent or with other solute atoms (“unsatisfied” polar groups). We expect that in future, SHO will enable higher-resolution predictions for a variety of molecular modeling applications.

A Covalent‐Like Feature of Intermolecular Hydrogen Bonding in Energetic Molecules 3,6‐Dihydrazino‐s‐tetrazine (DHT)

“…As one of the important intermolecular interactions, Hbonding is also critical in other aspects, such as biological structure and function, semiconductor properties. [25][26][27][28][29][30] From the classical perspective, its essence is electrostatic interaction or dipole-dipole forces; [31,32] however, several recent experimental and theoretical studies have presented different views. [33][34][35][36][37][38] The dominating "electrostatic factors" must be strongly antagonistic to H-bond formation, which was demonstrated by studying a class of H-bond complexes between closed-shell ions of similar charge.…”

Simulating Biomolecules: Festschrift to commemorate the 60th birthday of Charles L. Brooks III

“…Karanicolas presents a new model of polar desolvation for biomolecular energetics that he termed "solvent hydrogen-bond occlusion". [18] Feig incorporates a van der Waals term into his heterogeneous dielectric generalized Born model (HDGBvdW) and shows improved association energetics of membrane-embedded transmembrane helices. [19] Chen develops an optimization protocol of the GBMV2 implicit solvent force field for accurate simulation of protein conformational equilibria.…”

“…An open source distributed software package Poisson‐Boltzmann Analytical Method (PB‐AM) is presented by Head‐Gordon (Charlie's first PhD student) and her co‐workers in their paper; the approach comprises a fully analytical solution to the linearized Poisson Boltzmann equation. Karanicolas presents a new model of polar desolvation for biomolecular energetics that he termed “solvent hydrogen‐bond occlusion” . Feig incorporates a van der Waals term into his heterogeneous dielectric generalized Born model (HDGBvdW) and shows improved association energetics of membrane‐embedded transmembrane helices .…”

ВЗАИМОДЕЙСТВИЕ НУКЛЕИНОВЫХ КИСЛОТ С Молеку-Лами ВОДЫ, БЕЛКОВ И ИНТЕРКАЛЯТОРОВ (Обзор)

“…В воде растворены все биоорганические компоненты и вещества внутри клетки. Это высокополярный растворитель, необходимый для всех живых организмов (1)(2)(3). Нуклеиновые кислоты хорошо растворяются в воде (4,5).…”

“…Pace et al, 2004), through intercalation of aromatic amino acid side chains between base pairs, at which some specificity is also manifested (A. Bazzoli et al, 2017), and due to the direct binding of protein α-helices and β-layers in DNA grooves (E. Del Giudice et al, 2009). It is assumed that the latter type of interaction takes place, for example, in DNA complexes with the cro-repressor of gene expression and with a protein that activates catabolism, for which two models of the binding of α-helices with the left-sided and right-sided DNA double helix in the B-form have been proposed.…”