Assessing Uremic Toxin Binding Dynamics in Human Serum Albumin, Sudlow Site I

Abstract

In an effort to better understand the dynamics corresponding to the stabilization of uremic toxins such as indoxyl and p-cresyl sulfate, simulative modeling must be employed to observe molecular perambulations. In this investigation, the GROMACS molecular dynamics engine was used to perform a 250 ns simulation of human serum albumin complexed with these uremic toxins in its Sudlow Site I binding pocket. The trajectories were then taken and subjected to analyses designed to assess interaction energy and intermolecular distance between the amino acid residues that comprised the binding site. Intermolecular distance information was subjected to dimensionality reduction via primary component analysis, and then a mean-shift algorithm was employed to determine the most likely binding conformation, which was then cross referenced with the initial configuration from the experimentally-derived PDB file.