The Joint Solvation Interaction

TL;DR

This paper introduces the joint solvation interaction (JSI), a thermodynamic measure of solvent effects on flexible solutes, providing a formal definition, computational method, and comparison to existing concepts, with implications for understanding biological and self-assembly processes.

Contribution

The paper formalizes the JSI within the mixture expansion framework, relates it to rigid solute interactions, and proposes a molecular dynamics method for its computation.

Findings

JSI generalizes hydrophobic interactions.

Proposed method enables JSI calculation with free energy algorithms.

JSI is more useful than indirect solvent-mediated interactions for studying solute binding.

Abstract

The solvent-induced interactions (SII) between flexible solutes can be separated into two distinct components: the solvation-induced conformational effect, and the joint solvation interaction (JSI). The JSI quantifies the thermodynamic effect of the solvent simultaneously accommodating the solutes, generalizing the typical notion of the hydrophobic interaction. We present a formal definition of the JSI within the framework of the mixture expansion, demonstrate that this definition is equivalent to the SII between rigid solutes, and propose a method, partially-connected molecular dynamics, which allows one to compute the interaction with existing free energy algorithms. We also compare the JSI to the more natural generalization of the hydrophobic interaction, the indirect solvent-mediated interaction, and argue that JSI is a more useful quantity for studying solute binding thermodynamics. Direct calculation of the JSI may prove useful in developing our understanding of solvent effects in self-assembly, protein aggregation, and protein folding, for which the isolation of the JSI from the conformational component of the SII becomes important due to the intra-species flexibility.