Research Challenges

Specific Aim 1: We will develop and evaluate algorithms for structural clustering and dimensionality analysis of molecular dynamics trajectories of proteins. We will apply these tools to previously completed molecular dynamics trajectories of both intrinsically disordered and denatured natively folding proteins. The protein dynamics will be categorized based on comparisons of the estimated dimensionality in comparison to analytic polymer models.

Specific Aim 2: We will extend the algorithms for estimating the dimensionality of the space sampled in a protein trajectory to determine the volume and rate of sampling conformational space. This metric will be used to compare the trajectories of intrinsically disordered and denatured natively folding proteins. Additionally, this metric will be applied to evaluate differences in the coverage of conformational space for simulations using explicit versus implicit solvent models.