Revealing anti-fungal potential of plant-derived bioactive therapeutics in targeting secreted aspartyl proteinase (SAP) of Candida albicans: a molecular dynamics approach

Abstract

Candida species have established themselves as a major source of nosocomial infections. Increased expression of secreted aspartyl proteinases (SAP5) plays a crucial role in the pathogenesis of Candida species. Phytotherapeutics continue to serve as a viable resource for discovering novel antifungal agents. Hence the main aim of the present investigation is to explore the possible inhibitory role of the selected bioactive molecules against the SAP5 enzyme of C. albicans using in silico approach. Molecular docking and dynamic simulations were utilized to predict the binding affinity of the lead molecules using the AutoDock and Gromacs in-silico screening tools. Results of preliminary docking simulations show that the compounds hesperidin, vitexin, berberine, adhatodine, piperine, and chlorogenic acid exhibit significant interactions with the core catalytic residues of the target protein. The best binding ligands (hesperidin, vitexin, fluconazole) were subjected to molecular dynamics (MD) and essential dynamics of the trajectories. Results of the MD simulation confirm that the ligand-protein complexes became more stable from 20 ns until 100 ns. The calculated residue-level contributions to the interaction energy along a steady simulation trajectory of all three hits (hesperidin (−132.720 kJ/mol), vitexin (−83.963 kJ/mol) and fluconazole (−98.864 kJ/mol)) ensure greater stability of the leads near the catalytic region. Essential dynamics of PCA and DCCM analysis signifies that the binding of hesperidin and vitexin created a more structurally stable environment in the protein target. The overall outcomes of this study clearly emphasize that the bioactive therapeutics found in medicinal herbs may have remarkable scope in managing Candida infection.

Communicated by Ramaswamy H. Sarma

Keywords:

• Candida albicans
• secreted aspartyl proteinases
• medicinal herbs
• docking studies
• molecular dynamics
• antifungal

Acknowledgements

The authors wish to acknowledge their thanks to The School of Energy Technology, Pandit Deendayal Energy University, Gujarat, India, the Indian Council of Medical Research (ICMR), Government of India, New Delhi, India and the Noble Research Solution, Chennai, Tamil Nadu, India for their support.

Authors’ contributions

SD involved in Conceptualization, Methodology/Study design, Software, Validation, Formal analysis, Investigation, Resources, Data curation, Writing – original draft, Writing – review and editing, Visualization and Project administration. The author PPS involved in Conceptualization, Software, Validation, Investigation, Resources, Data curation, Writing – review and editing and Visualization. The author SSM involved in Conceptualization, Validation, Investigation, Writing – review and editing, Visualization and Supervision. The author VDS involved in Conceptualization, Validation, Investigation, Writing – review and editing. The author SJ involved in Validation, Investigation, Writing – review and editing

All authors read and approved the final version of the manuscript.

Disclosure statement

The authors declare no conflict of interest, financial or otherwise.

Additional information

Funding

This research did not receive any particular grant from funding agencies in the public, commercial, or not-for-profit sectors.