GA 2017

Platelet-activating factor (PAF) is a well-known regulator to be involved in the body's inflammatory response as well as vascular diseases such as thrombosis [1]. Currently, the use of computational techniques has been widely used particularly in the pharmacology field to establish the conceivable interaction mode of a molecule within the active site of a protein [2]. Such approach becomes as useful tool for establishing the interaction/activity of compounds within the active site of PAF-receptor [3]. Thus, as part of our research on PAF-receptor inhibitors, 85 naturally-occurring neolignans were in-vitro and in-silico evaluated (molecular docking, molecular dynamics and 3DQSAR) in order to establish their binding mode and determine its potentiality as PAF-antagonists. Stability of complexes between PAF-receptor and neolignans were investigated through Vina scores, selected residues interactions, and RMSD and RMSF profiles. Good Vina scores were obtained for receptor-ligand complexes interactions at different levels as well as good stabilization across 15 ns for several neolignans. Best poses were found to be different for each type of neolignan as well as the active site residues involved into the ligand-receptor binding. IC₅₀ values, docking scores and quantum properties were used as molecular descriptors along with the steric and electrostatic field values for PLS analysis. CoMFA model exhibited good statistical measure from PLS (q² = 0.821) indicating as an useful tool for the prediction of test set as well as newly designed/homologous structures against PAF-receptor based on neolignans. This is the first study to provide an explanation at atomic level of binding of neolignan-related compounds within this receptor. Work derived from Project IMP-CIAS-2293 financed by Vicerrectoría de Investigaciones at UMNG - Validity 2017. References: [1] Ishii S. et al. Prostag Other Lipid Mediat 2002; 68-69:599–609; [2] Sliwoski G. et al. Pharmacol Rev 2014; 66:334–395; [3] Gui C. et al. Proteins 2007; 67:41–52.