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Molecular Dynamics Simulations and Related Methods in Drug Discovery and Development

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Special Issue Editor

Special Issue Information

Dear Colleagues,

Molecules that have the potential to be delivered to a biopolymer responsible for pathological states associated with a disease can be developed as therapeutic agents. Such molecules have to overcome relevant biological barriers and establish intermolecular interactions with the active sites of the biopolymer. The process of drug discovery and development entails the identification of potential therapeutic agents and the design of optimal formulations for targeted or prolonged drug release in vivo. This requires a balanced dynamic interplay of intermolecular interactions of the therapeutic agent with different molecular systems in various environments. Computational methods, including molecular dynamics simulation and associated techniques, complement experimental methods in the evaluation of relevant processes at different stages of drug development or in the elucidation of their mechanisms.

This Special Issues is open to research articles and reviews focused on the application of molecular dynamics and related methods in drug discovery and medicine development.

Prof. Dr. Mire Zloh
Guest Editor

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Keywords

Computer aided molecular design
Protein-ligand interaction
Overcoming biological barriers
Mechanism of action
Targeted and prolonged drug release

Published Papers (1 paper)

Research

14 pages, 2243 KiB

Open AccessArticle

Computational Identification of BCR-ABL Oncogenic Signaling as a Candidate Target of Withaferin A and Withanone

by Vidhi Malik, Navaneethan Radhakrishnan, Sunil C. Kaul, Renu Wadhwa and Durai Sundar

Biomolecules 2022, 12(2), 212; https://doi.org/10.3390/biom12020212 - 26 Jan 2022

Cited by 6 | Viewed by 2701

Abstract

Withaferin-A (Wi-A), a secondary metabolite extracted from Ashwagandha (Withania somnifera), has been shown to possess anticancer activity. However, the molecular mechanism of its action and the signaling pathways have not yet been fully explored. We performed an inverse virtual screening to investigate its binding potential to the catalytic site of protein kinases and identified ABL as a strong candidate. Molecular docking and molecular dynamics simulations were undertaken to investigate the effects on BCR-ABL oncogenic signaling that is constitutively activated yielding uncontrolled proliferation and inhibition of apoptosis in Chronic Myeloid Leukemia (CML). We found that Wi-A and its closely related withanolide, Withanone (Wi-N), interact at both catalytic and allosteric sites of the ABL. The calculated binding energies were higher in the case of Wi-A at catalytic site (−82.19 ± 5.48) and allosteric site (−67.00 ± 4.96) as compared to the clinically used drugs Imatinib (−78.11 ± 5.21) and Asciminib (−54.00 ± 6.45) respectively. Wi-N had a lesser binding energy (−42.11 ± 10.57) compared to Asciminib at the allosteric site. The interaction and conformational changes, subjected to ligand interaction, were found to be similar to the drugs Imatinib and Asciminib. The data suggested that Ashwagandha extracts containing withanolides, Wi-A and Wi-N may serve as natural drugs for the treatment of CML. Inhibition of ABL is suggested as one of the contributing factors of anti-cancer activity of Wi-A and Wi-N, warranting further in vitro and in vivo experiments. Full article

(This article belongs to the Special Issue Molecular Dynamics Simulations and Related Methods in Drug Discovery and Development)

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