protein-binding

Characterization of ArkA Segment 1 to SH3 Binding using Markov State Models

Abstract

An SH3 domain is an interaction domain involved in a large number of the cellular processes responsible for signal transduction or supramolecular complex formation. To function, SH3 domains interact with intrinsically disordered proteins (IDPs). However, these IDPs bind in multiple steps, making the characterization of their full binding pathway a difficult task to complete with experiments alone. To better understand how such interactions contribute to cellular function, we used Molecular Dynamics to simulate the domain-peptide interaction between the peptide ArkA12 and domain AbpSH3. Hidden Markov state models were further used to define separate bound states and their specific transition rates on statistically relevant timescales. Preliminary work suggests that similar analytical methods using different sample features may produce results with improved prediction performance and computational efficiency.