Thermodynamics of a Coiled-Coil Protein Structure

Abstract

A coiled-coil protein structure consists of two or more interacting α-helical strands that together form a supercoil structure. Coiled-coil structures entail unique mechanical properties critical to the function and integrity of various motor proteins, cytoskeletal filaments and extra-cellular matrix proteins. The main objective of our work is to develop a statistical mechanical model to predict the propensity of a protein sequence to form an isolated coiled-coil structure and to study its structural response to the mechanical load. We develop a partition function for coiled-coil dimerization to estimate the probability of a given amino acid sequence to form various dimeric coiled-coil structures. We use our model's predictions to reexamine the assumptions of the thermodynamic models employed to obtain various free energy terms from the experimental measurements. The model parameters will be optimized based on comparisons with our experimental data of coiled-coil forming sequences designed to quantify various free energy effects. We will combine the above coiled-coil dimerization model with our previously developed model on the tensile mechanics of α-helical polypeptide. This results in a model that predicts the structural response of a given coiled-coil motif to a mechanical tension.