In Silico Characterization of Structural Distinctions between Isoforms of Human and Mouse Sphingosine Kinases for Accelerating Drug Discovery.

ABSTRACT: Alterations in cellular signaling pathways are associated with multiple disease states including cancers and fibrosis. Current research efforts to attenuate cancers, specifically lymphatic cancer, focus on inhibition of two sphingosine kinase isoforms, sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2). Determining differences in structural and physicochemical binding site properties of SphKs is attractive to refine inhibitor potency and isoform selectivity. This study utilizes a predictive in silico approach to determine key differences in binding sites in SphK isoforms in human and mouse species. Homology modeling, molecular docking of inhibitors, analysis of binding pocket residue positions, development of pharmacophore models, and analysis of binding cavity volume were perfo

SUBMITTER: Worrell BL 

PROVIDER: S-EPMC6734932 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature