AJ Life Sci. 2022, 5 (1)

In silico Analysis of PRODH Mutations and their biological significance in disease etiology

Muhammad Muzammal*1, Muzammil Ahmad Khan1,2, Sana Fatima1, Abida Bibi1, Shahzadi Raheela Anum1, Sumra Wajid Abbasi3, Ansar Ahmad Abbasi4, Iftikhar Ahmed1 and Syed Shakil Abbas1

1Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Khyber Pakhtunkhwa, Pakistan

2 Department of Human Genetics, Sidra Medical and Research Centre, Doha 26999, Qatar

3Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan

44Department of Zoology, Mirpur University of Science and Technology, Mirpur, AJK, Pakistan.


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




March 10, 2022

Received Revised

August 19, 2022


August 22, 2022

Available Online

September 17, 2022

Corresponding author email:


How to Cite

Abasyn Journal of Life Sciences , ISSN (online): 2663-1040, Published by Abasyn University