A geometric and topological analysis of the binding behavior of Intrinsically Disordered Proteins

Abstract

Intrinsically disordered proteins (IDPs) play vital regulatory roles in biology, emphasizing the significance of understanding their conformational behavior and interaction mechanisms during protein-ligand or protein-protein interactions. However, IDP analysis becomes difficult due to the lack of a stable structure. In this work, we investigate the binding behavior of an IDP using the surface information of the interacting protein complex. Our algorithm extracts the protein surface model’s topological and geometric features and predicts a geometrically favorable binding pose for an IDP around it. A transition path is planned to the predicted bound position to help evaluate the RMSD deviation in the IDP conformation structure. In our results, we use the Zernike descriptor metric to examine the structural homology of the binding pose and analyze the molar Gibbs free energy (binding affinity) of experimental conformation.