Computational Analysis of Wild-Type and Mutant CC2D2A Highlights Differential Binding Affinity

Khyber Ali; Saifullah; Shah Fahad Bin Ikram; Saad Ul Halim; Shahmeer Saleem; Warda Batool; Aisha Haq; Shabbir Ullah; Zain Ul Abideen; Sahar Nigar

doi:10.66222/IJACR.04.02.66

Authors

Khyber Ali Center of Biotechnology and Microbiology, University of Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan Author
Saifullah Center of Biotechnology and Microbiology, University of Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan Author
Shah Fahad Bin Ikram Center of Biotechnology and Microbiology, University of Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan Author
Saad Ul Halim Center of Biotechnology and Microbiology, University of Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan Author
Shahmeer Saleem Center of Biotechnology and Microbiology, University of Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan Author
Warda Batool Center of Biotechnology and Microbiology, University of Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan Author
Aisha Haq Center of Biotechnology and Microbiology, University of Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan Author
Shabbir Ullah Center of Biotechnology and Microbiology, University of Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan Author
Zain Ul Abideen Center of Biotechnology and Microbiology, University of Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan Author
Sahar Nigar Center of Biotechnology and Microbiology, University of Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan Author

DOI:

https://doi.org/10.66222/IJACR.04.02.66

Keywords:

CC2D2A; molecular docking; protein–ligand interaction; mutation analysis; hydrogen bonding; structural stability

Abstract

Background: CC2D2A is a key protein implicated in ciliopathies, and mutations may alter its structural stability and ligand-binding behavior. Understanding mutation-induced changes in protein–ligand interactions is essential for elucidating its functional impact.

Methods: Molecular docking analysis was performed to evaluate and compare ligand interactions with wild-type and mutant CC2D2A protein structures. Binding affinity, hydrogen bonding interactions, docking scores, and energy parameters were analyzed to assess structural and functional differences.

Results: The mutant CC2D2A protein exhibited improved binding affinity (S-score: −5.0838 kcal/mol) compared with the wild type (−4.6461 kcal/mol). The mutant formed four hydrogen bonds involving Asp1576, Arg1109, and Gln1108, whereas the wild-type protein formed only one hydrogen bond with Lys1216. Additionally, the mutant showed more favorable energy parameters, indicating enhanced ligand stability and stronger intermolecular interactions.

Conclusion: The mutation in CC2D2A significantly enhances ligand-binding affinity and interaction stability by increasing hydrogen bonding and improving docking energetics. These structural alterations suggest a potential functional impact of the mutation on protein activity.