In silico binding analysis of human CD40 ligand mimetic molecule, 3-(dimethylamino)-1-phenyl-1-propanone hydrochloride (3-DPH), with CD40 receptor molecules of various mammalian species

Abstract

Aim: To investigate the binding of human CD40 ligand (CD40L) mimetic molecule, 3-(dimethylamino)-1-phenyl-1-propanone hydrochloride (3-DPH), with CD40 receptor (CD40R) molecules of Homo sapiens, Cavia porcellus, Cricetulus griseus, Macaca mulatta, Mus musculus, Oryctolagus cuniculus, Papio anubis and Rattus norvegicus species using bioinformatics tool. Methodology: Three-dimensional structures of CD40Rs and CD40Ls for various mammalian species were generated using the published crystal structure of human CD40 receptor-ligand complex by homology modelling using SWISS-MODEL tool. Furthermore, human CD40L mimetic molecule, 3-DPH was docked against the generated CD40R of various mammalian species using AUTODOCK 4.2. Results: Docking studies revealed that documented HIS78 and GLN79 residues of human CD40R were the key interaction residues, which interacted with human CD40L and 3-DPH. The CD40Rs of H. sapiens, C. porcellus, C. griseus, M. mulatta, M. musculus, O. cuniculus, P. anubis, and R. norvegicus bind with 3-DPH with a binding energy -4.67, -5.22, -5.19, -4.62, -4.85, -4.63, -4.51, and -4.86 kcal/mol, respectively. Interpretation: Molecular docking studies provide crucial insight into the binding affinity and interaction of 3-DPH at the active site of CD40R of the respective mammalian species. O. cuniculus and M. musculus species were found to be appropriate animal models for further evaluation of the therapeutic effect of human CD40L mimetic molecule Key words: 3-DPH, Animal model, CD40R, CD40L, Homo sapeins, Molecular docking