Free Energy Analysis of Protein Folding and Adsorption at the Air/Water Interface

Abstract

Proteins are biological polymers that play many important roles in biological systems The protein functions are highly correlated with the protein structures which are affected by the solvent pH temperature and concentrations etc Protein have been applied in various fields such as the substrate surface modifications or the detecting molecules in the biosensors In order to probe the effects of adsorbed interface on the protein structures we investigate the protein conformational changes at the air/water interfaces for four different groups of proteins with different secondary structural characteristics i e ?-helix native β-hairpin native protein with equal ?- and β-probability and small amyloid peptide fibrils We applied molecular dynamics combined with methadyanmics to calculate the protein conformational free energies in bulk water and at air/water interface Furthermore we developed a thermodynamics model for protein adsorption that focuses on two contributions i e the desolvation of peptide residues and the reduction of air-water interfacial energy Via the comparison between the peptide adsorption free energies at the air/water interface obtain by the theoretical prediction and simulation data we found the proposed thermodynamic model accurately predicted the relative adsorption free energies of peptide in different conformations Combining the protein adsorption free energies estimated from the thermodynamic model and the conformational free energy calculated from MD simulations the complete thermodynamic cycle of protein adsorption and conformational change can be constructed The results showed that the air/water interfacial energy changes caused by the peptide allocation at the interface that inclines the air/water contact are the main driving force of the protein adsorbing at the interface Furthermore the stability of protein secondary structure is also affected by the desolvation of the amino acid exposed to the air phase Hence the peptide sequence is important for the protein secondary structural preference at the interface The model was further applied to investigate the adsorption free energy of small amyloid peptide fibrils Our results showed that owing to the arrangement of hydrophobic residues the adsorbing fibril face play important roles for amyloid fibril adsorption at the air/water interface

Date of Award	2017 Feb 14
Original language	English
Supervisor	Chi-cheng Chiu (Supervisor)