High-Throughput Virtual Screening of Proteins Using GRDE Molecular Interaction Fields

摘要

A new computational algorithm for protein binding sites characterization and comparison has been developed, which uses a common reference framework of the projected ligand-space four-point pharmacophore fingerprints, includes cavity shape. and can be used with diverse proteins as no structural alignment is required. Protein binding sites are first described using GRDE molecular interaction fields (GRDE-MIFs), and the FLAP (fingerprints for ligands and proteins) method is then used to encode and compare this information. The discriminating power of the algorithm and its applicability for large-scale protein analysis was valDEated by analyzing various scenarios: clustering of kinase protein families in a relevant manner, predicting ligand activity across related targets, and protein-protein Virtual screening. In all cases the results showed the effectiveness of the GRDE-FLAP method and its potential use in applications Such as DEentifying selectivity targets and tools/hits for new targets via the DEentification of other proteins with pharmacophorically similar binding sites.