In the present study, we performed in silico analysis on all reported mutations of PRODH in order to investigate their biological significance. 3D models of wildtype and mutant PRODH were predicted using I-TASSER. Protein-protein docking was done with Cluspro, while protein-substrate docking was done with Auto Dock tools. Alignment of 3D models (various mutant with wildtype) revealed that Arg185Gln (73.83%) and Gln19Term (6.25%) had the highest and lowest similarity indices, respectively. Enzyme pocket prediction identified the second largest active site pocket containing substrate proline binding residues Leu527, Tyr548, and Arg563. Moreover, docking of mutant and wildtype PRODH with its close interactor ALDH4A1 showed differences with respect to position and nature of interacting amino acids residues. We observed that the nature of amino acid substitution and the number of bonds affect the binding of proline molecule with enzyme, and therefore, affect its biological activity.
Keywords: PRODH, proline dehydrogenase enzyme, in silico analysis, modeling and docking, biological significance