Solvent Molecule Bondability and Effect on Mechanical Proteins Transition State and Stability - A Smd Study

Abstract

The solvent environment plays an integral role in physiological processes in the living cell. Changes in solvent environment or properties are a chemical signal that may induce changes in the mechanical response in a protein system. In this steered molecular dynamics study, using simulations we stretch to unfold the mechanical protein titin in aqueous and non-aqueous environment and reveal the atomic details and mechanism of interactions between solvent and proteins when subjected to steering force. Titin is a mechanically stable protein which is able to resist force due to a force bearing topology element - antiparallel beta sheet, stabilized by 6 native hydrogen bond contacts. In our study we observe individual solvent molecules bridging the stabilizing native hydrogen bonds in the force bearing patch. Solvent molecules also modulate the distance to the transition state. We investigate the distance to transition state of the unfolding reaction as related to solvent molecule size and we also introduce the concept of solvent molecule bondability - the capability of a solvent molecule to bridge the native hydrogen bond contact in more than one way, as determined by solvent molecule polarity and topology. Features of the simulations were also matched with previously reported experimental results.Since The distance to transition state determines the mechanical stability of a protein, changing the solvent composition is a novel way to fine tune mechanical properties. Our investigation provides insights of the properties of the unfolding reaction pathway and possible mechanisms of mechanical protection when such proteins are subject to mechanical stress.