U.S. Army Research Laboratory (ARL) XPairIt Simulator for Peptide Docking and Analysis

: Identifying the natural orientation of a peptide bound to a protein via computational means presents unique obstacles not often encountered in the more common searches of ligand-protein or protein-protein complexes. Along with a brief review of the current state of methods in these simulations, we introduce software to tackle many of the challenges that still exist. These hurdles are addressed with the XPairIt API, a docking protocol which unites powerful open source simulation packages and enhances the representation of energetics and flexibility within a simulation. Ability of the protocol is demonstrated through a global docking case study, and we show improvement in binding energy with the combined use of molecular dynamics and Monte Carlo docking. Comparison of methodology and final root mean squared displacement (RMSD) of our bound structures to previous work is made, and we highlight improvements in peptide and protein flexibility.