title: Pharmacophore modelling: a forty year old approach and its modern synergies.
abstract: A pharmacophore represents a simple and intuitive concept that can be used in many different drug discovery applications. Ligand-based and structure-based pharmacophore models continue to play a pivotal role in hit discovery and may guide lead optimization. Moreover, owing to the versatility of the pharmacophore concept, pharmacophore modelling has been routinely used in combination with other molecular modelling techniques. The synergistic use of different tools in drug discovery workflows may allow to fully exploit the advantages, while compensating for some of the intrinsic limitations, of each methodology. This review will focus on the synergistic combination of pharmacophore modelling with other molecular modelling approaches such as the hot spot analysis of protein binding sites, molecular dynamics, and docking.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Modena e Reggio Emilia, Via Campi 183, 41100, Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Caporuscio
authors.forename: A
authors.initials: A
authors.lastname: Tafi
mesh_terms: D001665:Binding Sites; D015704:CD4 Antigens / Q000737:chemistry; D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D016333:HIV Protease / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011955:Receptors, Drug / Q000737:chemistry*; D012984:Software
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D008024:Ligands; D004364:Pharmaceutical Preparations; D011955:Receptors, Drug; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1