Computational screening of chemical constituents derived from berry fruits as allosteric caspace-3/-7 inhibitors

Waseem Ahmad Ansari; Mohsin Ali Khan; S M Mahfooz Hasan; Zainab Siddiqui; Saheem Ahmad; Mohd Shahnawaz Khan; Mohammad Faheem Khan

doi:10.1007/s13205-024-04067-7

Computational screening of chemical constituents derived from berry fruits as allosteric caspace-3/-7 inhibitors

3 Biotech. 2024 Oct;14(10):234. doi: 10.1007/s13205-024-04067-7. Epub 2024 Sep 16.

Authors

Waseem Ahmad Ansari¹, Mohsin Ali Khan², S M Mahfooz Hasan², Zainab Siddiqui², Saheem Ahmad³, Mohd Shahnawaz Khan⁴, Mohammad Faheem Khan^{1

5}

Affiliations

¹ Department of Biotechnology, Era's Lucknow Medical College & Hospital, Era University, Sarfarazganj, Hardoi Road, Lucknow, 226003 India.
² Center for Disease Mapping and Therapeutic Research, Era's Lucknow Medical College & Hospital, Era University, Sarfarazganj, Hardoi Road, Lucknow, 226003 India.
³ Department of Medical Laboratory Science, College of Applied Medical Sciences, University of Hail, 2440 Hail, Saudi Arabia.
⁴ Department of Biochemistry, College of Sciences, King Saud University, 12371 Riyadh, Saudi Arabia.
⁵ Department of Chemistry, Era University, Sarfarazganj, Hardoi Road, Lucknow, 226003 India.

PMID: 39297056
PMCID: PMC11405617 (available on 2025-10-01)
DOI: 10.1007/s13205-024-04067-7

Abstract

With the aim of finding the plant-derived allosteric inhibitors of caspase-3/-7, we conducted computational investigations of bioactive compounds present in various berry fruits. In a molecular docking study, perulactone demonstrated excellent binding affinity scores of -12.1 kcal/mol and -9.1 kcal/mol for caspase 7 and 3, respectively, whereas FDA-approved allosteric inhibitors (DICA and FICA) were found to show lower docking scores (-5.6 and -6.1 kcal/mol) against caspase 7 while (-5.0 and -5.1 kcal/mol) for caspase 3, respectively. MD simulations were used to validate the binding stability of perulactone in the active sites of caspase-7/-3, and the results showed outstanding stability with lower ligand RMSDs of 1.270-3.088 Å and 2.426-9.850 Å against the targeted receptor. Furthermore, we performed MMGBSA free binding energy, where the perulactone values of ΔG _Bind were determined to be -63.98 kcal/mol and -66.32 kcal/mol for both receptors (3IBF and 1NME), which are significantly better than the -45.16 kcal/mol and -39.51 kcal/mol for DICA as well as -26.37 kcal/mol and -15.50 kcal/mol for FICA, respectively. The drug resemblance of perulactone was effectively evaluated by ADMET. Thus, our findings indicated that perulactone could be an orally administered therapeutic candidate for regulating apoptosis in a variety of disorders. However, there may be an urgent need to study using in vitro and in vivo experiments.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04067-7.

Keywords: Allosteric site; Berry fruits; MMGBSA calculation; Molecular docking; Molecular dynamic simulation.

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