Exploring Protein-Ligand Interactions to Increase the Binding Action of Kynurenic Acid to GPR35

School Name

South Carolina Governor's School for Science and Mathematics

Grade Level

12th Grade

Presentation Topic

Biochemistry

Presentation Type

Mentored

Abstract

The g-protein coupled receptor 35, or GPR35, is the receptor responsible for the initiation of the chemokine-mediated signaling pathway in humans, expressed primarily in the duodenum and small intestine. GPR35 has been demonstrated to protect against neuroinflammation and play a major role in extending lifespans. While much is unknown regarding the physiological mechanisms of GPR35, it has become an area of interest in targeting inflammation and gastrointestinal pathology, as it shows promising results in reducing vasoconstrictive responses and allergic reactions. Kynurenic acid, a derivative of L-tryptophan, is a primary ligand to GPR35. When bound to the active site of GPR35, kynurenic acid produces various neurological and gastrointestinal effects. Ligands that bind to the same binding site on GPR35 are kynurenic acid, lodoxamide, and zaprinast. Through protein docking in the Schrödinger Maestro software, docking scores were first calculated for the unaltered compounds. Kynurenic acid originally produced a docking score of –8.697 kcal/mol, lodoxamide originally produced a docking score of –14.152 kcal/mol, and zaprinast originally produced a docking score of –7.495 kcal/mol. Through examining a ligand interaction diagram, the importance of oxygens and the high hydrophobicity of kynurenic acid were examined. Using this data, multiple alcohol groups were added to counter the hydrophobic nature of kynurenic acid while keeping the oxygens constant to preserve the previously established amino-acid interactions. Kynurenic acid’s docking score was improved from –8.697 kcal/mol to –15.604 kcal/mol, showing an improvement in kynurenic acid’s binding to GPR35.

Location

RITA 363

Start Date

3-23-2024 10:45 AM

Presentation Format

Oral Only

Group Project

No

COinS
 
Mar 23rd, 10:45 AM

Exploring Protein-Ligand Interactions to Increase the Binding Action of Kynurenic Acid to GPR35

RITA 363

The g-protein coupled receptor 35, or GPR35, is the receptor responsible for the initiation of the chemokine-mediated signaling pathway in humans, expressed primarily in the duodenum and small intestine. GPR35 has been demonstrated to protect against neuroinflammation and play a major role in extending lifespans. While much is unknown regarding the physiological mechanisms of GPR35, it has become an area of interest in targeting inflammation and gastrointestinal pathology, as it shows promising results in reducing vasoconstrictive responses and allergic reactions. Kynurenic acid, a derivative of L-tryptophan, is a primary ligand to GPR35. When bound to the active site of GPR35, kynurenic acid produces various neurological and gastrointestinal effects. Ligands that bind to the same binding site on GPR35 are kynurenic acid, lodoxamide, and zaprinast. Through protein docking in the Schrödinger Maestro software, docking scores were first calculated for the unaltered compounds. Kynurenic acid originally produced a docking score of –8.697 kcal/mol, lodoxamide originally produced a docking score of –14.152 kcal/mol, and zaprinast originally produced a docking score of –7.495 kcal/mol. Through examining a ligand interaction diagram, the importance of oxygens and the high hydrophobicity of kynurenic acid were examined. Using this data, multiple alcohol groups were added to counter the hydrophobic nature of kynurenic acid while keeping the oxygens constant to preserve the previously established amino-acid interactions. Kynurenic acid’s docking score was improved from –8.697 kcal/mol to –15.604 kcal/mol, showing an improvement in kynurenic acid’s binding to GPR35.