Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery

Autor:	Alexander, Heifetz, Michelle, Southey, Inaki, Morao, Andrea, Townsend-Nicholson, Mike J, Bodkin
Rok vydání:	2017
Předmět:	Models Molecular Molecular Docking Simulation Drug Discovery Computational Biology Quantitative Structure-Activity Relationship Water Computer Simulation Molecular Dynamics Simulation Ligands Software Protein Binding Receptors G-Protein-Coupled Workflow
Zdroj:	Methods in molecular biology (Clifton, N.J.). 1705
ISSN:	1940-6029
Popis:	GPCR modeling approaches are widely used in the hit-to-lead (H2L) and lead optimization (LO) stages of drug discovery. The aims of these modeling approaches are to predict the 3D structures of the receptor-ligand complexes, to explore the key interactions between the receptor and the ligand and to utilize these insights in the design of new molecules with improved binding, selectivity or other pharmacological properties. In this book chapter, we present a brief survey of key computational approaches integrated with hierarchical GPCR modeling protocol (HGMP) used in hit-to-lead (H2L) and in lead optimization (LO) stages of structure-based drug discovery (SBDD). We outline the differences in modeling strategies used in H2L and LO of SBDD and illustrate how these tools have been applied in three drug discovery projects.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::671852008e9d402bb1eb5638e81c056a https://pubmed.ncbi.nlm.nih.gov/29188574 Zobrazit plný text záznamu