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Mitogen activated protein kinase-1 and cell division control protein-42 are putative targets for the binding of novel natural lead molecules: a therapeutic intervention against Candida albicans.
J Biomol Struct Dyn. 2020 Sep; 38(15):4584-4599.JB

Abstract

Candida albicans, fungal yeast causes several lethal infections in immune-suppressed patients and recently emerged as drug-resistant pathogens worldwide. The present study aimed to screen putative drug targets of Candia albicans and to study the binding potential of novel natural lead compounds towards these targets by computational virtual screening and molecular dynamic (MD) simulation. Through extensive analysis of mitogen-activated protein kinase (MAPK) signalling pathways, mitogen-activated protein kinase-1 (HOG1) and cell division control protein-42 (CDC42) genes were prioritized as putative targets based on their virulent functions. The three-dimensional structures of these genes, not available in their native forms, were computationally modeled and validated. 76 lead molecules from various natural sources were screened and their drug likeliness and pharmacokinetic features were predicted. Among these ligands, two lead molecules that demonstrated ideal drug-likeliness and pharmacokinetic features were docked against HOG1 and CDC42 and their binding potential was compared with the binding of conventional drug Fluconazole with their usual target. The prediction was computationally validated by MD simulation. The current study revealed that Cudraxanthone-S present in Cudrania cochinchinensis and Scutifoliamide-B present in Piper scutifolium exhibited ideal drug likeliness, pharmacokinetics and binding potential to the prioritized targets in comparison with the binding of Fluconazole and their usual target. MD simulation showed that CDC42-Cudraxanthone-S and HOG1-Scutifoliamide-B complexes were exhibited stability throughout MD simulation. Thus, the study provides significant insight into employing HOG1 and CDC42 of MAPK as putative drug targets of C. albicans and Cudraxanthone-S and Scutifoliamide-B as potential inhibitors for drug discovery.Communicated by Ramaswamy H. Sarma.

Authors+Show Affiliations

Department of Biotechnology, Dayananda Sagar College of Engineering, Kumaraswamy Layout, Bengaluru, India.Department of Biotechnology, Dayananda Sagar College of Engineering, Kumaraswamy Layout, Bengaluru, India. Department of Biotechnology, RV College of Engineering, Bangalore, Karnataka, India.Department of Biotechnology, Dayananda Sagar College of Engineering, Kumaraswamy Layout, Bengaluru, India.Department of Biotechnology, RV College of Engineering, Bangalore, Karnataka, India.Department of Biotechnology, Dayananda Sagar College of Engineering, Kumaraswamy Layout, Bengaluru, India.Department of Biotechnology, Dayananda Sagar College of Engineering, Kumaraswamy Layout, Bengaluru, India.Department of Biotechnology, Dayananda Sagar College of Engineering, Kumaraswamy Layout, Bengaluru, India.Department of Biotechnology, Dayananda Sagar College of Engineering, Kumaraswamy Layout, Bengaluru, India.Department of Biotechnology, RV College of Engineering, Bangalore, Karnataka, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31625462

Citation

Gopal, Dharshini, et al. "Mitogen Activated Protein Kinase-1 and Cell Division Control Protein-42 Are Putative Targets for the Binding of Novel Natural Lead Molecules: a Therapeutic Intervention Against Candida Albicans." Journal of Biomolecular Structure & Dynamics, vol. 38, no. 15, 2020, pp. 4584-4599.
Gopal D, Muddebihalkar AG, Skariyachan S, et al. Mitogen activated protein kinase-1 and cell division control protein-42 are putative targets for the binding of novel natural lead molecules: a therapeutic intervention against Candida albicans. J Biomol Struct Dyn. 2020;38(15):4584-4599.
Gopal, D., Muddebihalkar, A. G., Skariyachan, S., C, A. U., Kaveramma, P., Praveen, U., Shankar, R. R., Venkatesan, T., & Niranjan, V. (2020). Mitogen activated protein kinase-1 and cell division control protein-42 are putative targets for the binding of novel natural lead molecules: a therapeutic intervention against Candida albicans. Journal of Biomolecular Structure & Dynamics, 38(15), 4584-4599. https://doi.org/10.1080/07391102.2019.1682053
Gopal D, et al. Mitogen Activated Protein Kinase-1 and Cell Division Control Protein-42 Are Putative Targets for the Binding of Novel Natural Lead Molecules: a Therapeutic Intervention Against Candida Albicans. J Biomol Struct Dyn. 2020;38(15):4584-4599. PubMed PMID: 31625462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitogen activated protein kinase-1 and cell division control protein-42 are putative targets for the binding of novel natural lead molecules: a therapeutic intervention against Candida albicans. AU - Gopal,Dharshini, AU - Muddebihalkar,Aditi G, AU - Skariyachan,Sinosh, AU - C,Akshay Uttarkar, AU - Kaveramma,Prinith, AU - Praveen,Ulluvangada, AU - Shankar,Roshini Ravi, AU - Venkatesan,Tejaswini, AU - Niranjan,Vidya, Y1 - 2019/10/29/ PY - 2019/10/19/pubmed PY - 2019/10/19/medline PY - 2019/10/19/entrez KW - CDC42 KW - Candida albicans KW - HOG1 KW - cell division control protein 42 KW - computational virtual screening KW - cudraxanthone-S KW - mitogen activated protein kinase-1 KW - potential inhibitors KW - scutifoliamide-B SP - 4584 EP - 4599 JF - Journal of biomolecular structure & dynamics JO - J. Biomol. Struct. Dyn. VL - 38 IS - 15 N2 - Candida albicans, fungal yeast causes several lethal infections in immune-suppressed patients and recently emerged as drug-resistant pathogens worldwide. The present study aimed to screen putative drug targets of Candia albicans and to study the binding potential of novel natural lead compounds towards these targets by computational virtual screening and molecular dynamic (MD) simulation. Through extensive analysis of mitogen-activated protein kinase (MAPK) signalling pathways, mitogen-activated protein kinase-1 (HOG1) and cell division control protein-42 (CDC42) genes were prioritized as putative targets based on their virulent functions. The three-dimensional structures of these genes, not available in their native forms, were computationally modeled and validated. 76 lead molecules from various natural sources were screened and their drug likeliness and pharmacokinetic features were predicted. Among these ligands, two lead molecules that demonstrated ideal drug-likeliness and pharmacokinetic features were docked against HOG1 and CDC42 and their binding potential was compared with the binding of conventional drug Fluconazole with their usual target. The prediction was computationally validated by MD simulation. The current study revealed that Cudraxanthone-S present in Cudrania cochinchinensis and Scutifoliamide-B present in Piper scutifolium exhibited ideal drug likeliness, pharmacokinetics and binding potential to the prioritized targets in comparison with the binding of Fluconazole and their usual target. MD simulation showed that CDC42-Cudraxanthone-S and HOG1-Scutifoliamide-B complexes were exhibited stability throughout MD simulation. Thus, the study provides significant insight into employing HOG1 and CDC42 of MAPK as putative drug targets of C. albicans and Cudraxanthone-S and Scutifoliamide-B as potential inhibitors for drug discovery.Communicated by Ramaswamy H. Sarma. SN - 1538-0254 UR - https://www.unboundmedicine.com/medline/citation/31625462/Mitogen_activated_protein_kinase_1_and_cell_division_control_protein_42_are_putative_targets_for_the_binding_of_novel_natural_lead_molecules:_a_therapeutic_intervention_against_Candida_albicans_ L2 - http://www.tandfonline.com/doi/full/10.1080/07391102.2019.1682053 DB - PRIME DP - Unbound Medicine ER -
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