title: The interplay between molecular modeling and chemoinformatics to characterize protein-ligand and protein-protein interactions landscapes for drug discovery.
abstract: Protein-ligand and protein-protein interactions play a fundamental role in drug discovery. A number of computational approaches have been developed to characterize and use the knowledge of such interactions that can lead to drug candidates and eventually compounds in the clinic. With the increasing structural information of protein-ligand and protein-protein complexes, the combination of molecular modeling and chemoinformatics approaches are often required for the efficient analysis of a large number of such complexes. In this chapter, we review the progress on the developments of in silico approaches that are at the interface between molecular modeling and chemoinformatics. Although the list of methods and applications is not exhaustive, we aim to cover representative cases with a special emphasis on interaction fingerprints and their applications to identify "hot spots." We also elaborate on proteochemometric modeling and the emerging concept of activity landscape, structure-based interpretation of activity cliffs and structure-protein-ligand interaction relationships. Target-ligand relationships are discussed in the context of chemogenomics data sets.
authors.affiliation: Mayo Clinic, Scottsdale, Arizona, USA. Electronic address: MedinaFranco.Jose@mayo.edu.
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
authors.affiliation: Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Oscar
authors.initials: O
authors.lastname: Méndez-Lucio
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Karina
authors.initials: K
authors.lastname: Martinez-Mayorga
mesh_terms: D000818:Animals; D003198:Computer Simulation; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D048088:Informatics; D008958:Models, Molecular; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins
keywords: 2D interaction maps; 3D activity cliffs; Activity cliff generators; Hot spots; Interaction fingerprint; Pharmacophore; Protein–ligand interaction fingerprints; Proteochemometric modeling; Structure protein–ligand interaction relationships; Structure–activity relationships