Title of Abstract

In Silico Binding Analysis of a Zone 2 Modified Sphingosine Kinase Inhibitor

Session Title

Physical Sciences

Faculty Mentor

T. Christian Grattan, Ph.D.; grattanc@winthrop.edu

College

College of Arts and Sciences

Department

Chemistry, Physics & Geology

Faculty Mentor

T. Christian Grattan, Ph.D.

Abstract

Sphingosine-1-phosphate is a bioactive lipid mediator that has been shown to play a critical role in cell migration, survival, and proliferation. It is phosphorylated from sphingosine, which has the opposite effect on cells. Sphingosine inhibits cell proliferation and causes apoptosis. Sphingosine kinase is a lipid kinase that catalyzes the phosphorylation of sphingosine into sphingosine-1-phosphate. Sphingosine kinase has two isoenzymes, sphingosine kinase 1 and 2. Sphingosine kinase 1 is ubiquitously expressed in most cancer cells where it has been linked to cell proliferation, migration, and survival. Based on this information, sphingosine kinase 1 has become a novel target for anticancer therapy. We analyzed the molecular properties of several zone 2 inhibitors of sphingosine kinase inhibitor 1 using an online molecular property analysis site called “molinspiration”. The inhibitors were then modeled using the Marvin’s Sketch computer software. The inhibitors were then uploaded into USCF Chimera with sphingosine kinase 1 and the docking analysis was conducted using Autodock Vina. The binding energies of each inhibitor were recorded from the docking analysis. These docking energies evaluated how well each inhibitor was able to bind to the docking site in silico. The optimal binding energy was achieved by replacing the pyrazole ring linker in a known sphingosine kinase 1 inhibitor, SKI-1, with a 2,5-substituted pyridine ring system. This information will be useful when determining the optimized inhibitors for Zone 2 in conjuction with other optimized sites to improve binding and efficacy of a modified sphingosine kinase inhibitor 1.

Additional Fields About Your Abstract

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Course Assignment

MCNR 300 - Fortner-Wood

Grant Support

Support was provided by an NIH-INBRE grant from the National Center for Research Resources and the National Institute for General Medical Sciences as well as the Winthrop University Department of Chemistry, Physics, and Geology. McNair Scholars Program

Start Date

16-4-2021 3:00 PM

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Apr 16th, 3:00 PM

In Silico Binding Analysis of a Zone 2 Modified Sphingosine Kinase Inhibitor

Sphingosine-1-phosphate is a bioactive lipid mediator that has been shown to play a critical role in cell migration, survival, and proliferation. It is phosphorylated from sphingosine, which has the opposite effect on cells. Sphingosine inhibits cell proliferation and causes apoptosis. Sphingosine kinase is a lipid kinase that catalyzes the phosphorylation of sphingosine into sphingosine-1-phosphate. Sphingosine kinase has two isoenzymes, sphingosine kinase 1 and 2. Sphingosine kinase 1 is ubiquitously expressed in most cancer cells where it has been linked to cell proliferation, migration, and survival. Based on this information, sphingosine kinase 1 has become a novel target for anticancer therapy. We analyzed the molecular properties of several zone 2 inhibitors of sphingosine kinase inhibitor 1 using an online molecular property analysis site called “molinspiration”. The inhibitors were then modeled using the Marvin’s Sketch computer software. The inhibitors were then uploaded into USCF Chimera with sphingosine kinase 1 and the docking analysis was conducted using Autodock Vina. The binding energies of each inhibitor were recorded from the docking analysis. These docking energies evaluated how well each inhibitor was able to bind to the docking site in silico. The optimal binding energy was achieved by replacing the pyrazole ring linker in a known sphingosine kinase 1 inhibitor, SKI-1, with a 2,5-substituted pyridine ring system. This information will be useful when determining the optimized inhibitors for Zone 2 in conjuction with other optimized sites to improve binding and efficacy of a modified sphingosine kinase inhibitor 1.