Target‐based drug repurposing against Candida albicans—A computational modeling, docking, and molecular dynamic simulations study

Rashi Verma; Dibyabhaba Pradhan; Arnab Nayek; Harpreet Singh; Arun Kumar Jain; Luqman Ahmad Khan

doi:10.1002/jcb.30163

journal article Oct 21, 2021

Target‐based drug repurposing against Candida albicans—A computational modeling, docking, and molecular dynamic simulations study

Rashi Verma Dibyabhaba Pradhan Arnab Nayek Harpreet Singh

Arun Kumar Jain Luqman Ahmad Khan

Journal of Cellular Biochemistry Vol. 123 No. 2 pp. 289-305 · Wiley

View at Publisher Save 10.1002/jcb.30163

Abstract

AbstractThe emergence of multidrug‐resistant strains of Candida albicans has become a global threat mostly due to co‐infection with immune‐compromised patients leading to invasive candidiasis. The life‐threatening form of the disease can be managed quickly and effectively by drug repurposing. Thus, the study used in silico approaches to evaluate Food and Drug Administration (FDA) approved drugs against three drug targets—TRR1, TOM40, and YHB1. The tertiary structures of three drug targets were modeled, refined, and evaluated for their structural integrity based on PROCHECK, ERRAT, and PROSA. High‐throughput virtual screening of FDA‐approved drugs (8815), interaction analysis, and energy profiles had revealed that DB01102 (Arbutamine), DB01611 (Hydroxychloroquine), and DB09319 (Carindacillin) exhibited better binding affinity with TRR1, TOM40, and YHB1, respectively. Notably, the molecular dynamic simulation explored that Gln45, Thr119, and Asp288 of TRR1; Thr107 and Ser121 of TOM40; Arg193, Glu213, and Ser228 of YHB1 are crucial residues for stable drug‐target interaction. Additionally, it also prioritized Arbutamine‐TRR1 as the best drug‐target complex based on MM‐PBSA (−52.72 kcal/mol), RMSD (2.43 Å), and radius of gyration (−21.49 Å) analysis. In‐depth, PCA results supported the findings of molecular dynamic simulations. Interestingly, the conserved region (>70%) among the TRR1 sequences from pathogenic Candida species indicated the effectiveness of Arbutamine against multiple species of Candida as well. Thus, the study dispenses new insight and enriches the understanding of developing an advanced technique to consider potential antifungals against C. albicans. Nonetheless, a detailed experimental validation is needed to investigate the efficacy of Arbutamin against life‐threatening candidiasis.

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References

Details

Published: Oct 21, 2021
Vol/Issue: 123(2)
Pages: 289-305
License: View

Authors

R

Rashi Verma

Department of Biosciences Jamia Millia Islamia New Delhi India; Biomedical Informatics Centre Indian Council of Medical Research New Delhi India

D

Dibyabhaba Pradhan

Computational Genomics Centre, All India Institute of Medical Sciences Indian Council of Medical Research New Delhi India

A

Arnab Nayek

Department of Biochemistry All India Institute of Medical Sciences New Delhi India

H

Harpreet Singh

Computational Genomics Centre, All India Institute of Medical Sciences Indian Council of Medical Research New Delhi India

A

Arun Kumar Jain

Biomedical Informatics Centre Indian Council of Medical Research New Delhi India

L

Luqman Ahmad Khan

Department of Biosciences Jamia Millia Islamia New Delhi India

Funding

Indian Council of Medical Research Award: ISRM/11(30)/2019

Cite This Article

Rashi Verma, Dibyabhaba Pradhan, Arnab Nayek, et al. (2021). Target‐based drug repurposing against Candida albicans—A computational modeling, docking, and molecular dynamic simulations study. Journal of Cellular Biochemistry, 123(2), 289-305. https://doi.org/10.1002/jcb.30163

Target‐based drug repurposing against Candida albicans—A computational modeling, docking, and molecular dynamic simulations study

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