Fast Estimation of Protein Adsorption Free Energy at Interface via Molecular Dynamics Simulations

Abstract

Proteins are biopolymers with many important biological functions such as structural supports catalysis and cell signaling etc Applications of proteins e g sensors and biocatalysts require them to function at interfaces Since the function of a protein is directly related to its 3-dimentional folding structure understanding the protein conformational preference at the interface is critical for their application designs Previous study derived a fast and accurate estimation of protein conformational preference changes when adsorbed at air/water interface using molecular dynamics (MD) simulations and the experimental solvation free energy data Despite of the accurate estimation of the adsorption free energy difference between two protein conformations the value for each adsorption free energy is overestimated by 1-2 orders Here we re-derived the de-solvation and the interfacial energy terms to provide a more accurate adsorption free energy estimation Using MD simulation we mapped the solvent accessible surface area (SASA) with the ideal free energy to identify the direct relation between them This allowed us to construct the de-solvation free energy and SASA database for 20 amino acids allowing the further estimation of protein de-solvation free energy For the interfacial energy we corrected the surface tension using the factor k related to the effects of surface meniscus and line tension at interface The refined estimation resulted in greatly improved adsorption free energy estimations with less than 10% error for polyalanine and GB1 peptide in both ?–helix and β-hairpin conformations This model was further applied to investigate the adsorption free energy of small amyloid peptide fibrils at air/water interface Our results showed that the fibril tends to adsorb at the air/water interface due to the reduction of adsorption free energy from trimer to hexamer We also extended the new adsorption model to estimate adsorption free energy of protein at the water/DOPC bilayer interface The resulting energy profiles of ?-helical and β-strand polyalanine were in excellent agreement with the reference umbrella sampling free energy profiles

Date of Award	2020
Original language	English
Supervisor	Mei-Jywan Syu (Supervisor)