Scoring Protein-Substrate Complex Decoys Based on Electrostatic and Hydrophobic Complementarities: Evaluation of Hormone-Receptor Interactions

Abstract

Frequently, hitherto automatic systems for rigid body docking of a substrate into a receptor output series of protein-substrate decoys differing from each other in the orientation of the ligand molecule within the receptor cleft [3, 4, 5]. Then, using several schemes based mainly on the electrostatics of the atoms composing the cleft and the ligand, a scoring of the decoys is carried out, the most plausible structure being that with the highest score. Commonly used properties to score the decoys are the analysis of putative hydrogen bonds, ion-ion interactions, hydrophobic interaction and other electrophysical properties of the atoms, the evaluations being carried on an atomic bases which most of the time is costly in terms of processing times besides relying heavily on a specialist knowledge. Here we have developed a completely automatic method to perform the scoring of protein-substrate decoys, which is a combination of a well known pattern recognition method and a filtering process in order to detect complementary patterns from the electrostatic point of view of regions on the surfaces of both the ligand molecule and the protein cleft. The result is a swift and concise methodology to score the decoys by degree of electrostatic and hydrophobic complementarity.