Prediction of ligand binding using an approach designed to accommodate diversity in protein-ligand interactions.

Abstract

Computational determination of protein-ligand interaction potential is important for many biological applications including virtual screening for therapeutic drugs. The novel internal consensus scoring strategy is an empirical approach with an extended set of 9 binding terms combined with a neural network capable of analysis of diverse complexes. Like conventional consensus methods, internal consensus is capable of maintaining multiple distinct representations of protein-ligand interactions. In a typical use the method was trained using ligand classification data (binding/no binding) for a single receptor. The internal consensus analyses successfully distinguished protein-ligand complexes from decoys (r², 0.895 for a series of typical proteins). Results are superior to other tested empirical methods. In virtual screening experiments, internal consensus analyses provide consistent enrichment as determined by ROC-AUC and pROC metrics.