Surveying FDA-approved drugs as new potential inhibitors of N-cadherin protein: a virtual screening approach
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ORIGINAL RESEARCH
Surveying FDA-approved drugs as new potential inhibitors of N-cadherin protein: a virtual screening approach Sahar Khajeh 1 & Mahboobeh Eslami 2 & Navid Nezafat 2,3 & Zohreh Mostafavi-Pour 1,4 & Manica Negahdaripour 2,3 & Younes Ghasemi 2,3 & Vahid Razban 5,6 Received: 14 April 2020 / Accepted: 14 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Since N-cadherin protein plays a remarkable role in cancer metastasis and tumor growth and progression, finding new effective inhibitors of this protein can be of high importance in cancer treatment. Nevertheless, few molecules have been introduced to inhibit N-cadherin protein to date. In this work, in order to find and present potent inhibitors, 3358 FDA-approved small molecules were docked against N-cadherin protein. All complexes with binding energy − 9 to − 8 kcal/mol were selected for protein-ligand interaction analysis. In the following, Tanimoto coefficient (Tc) was calculated for those molecules that established appropriate interactions with N-cadherin in order to compute the similarity score between them. Afterwards, molecular dynamics simulation and free energy calculations were done to estimate the stability and ability of the chosen ligands in complex with the target protein. Finally, seven small molecules among 3358 FDA-approved were suggested as potential inhibitors of N-cadherin protein. Keywords N-cadherin . ADH-1 . Classical molecular dynamics simulations . Molecular docking . Tanimoto coefficient
Introduction Cadherins are the main molecules contributing to cell-cell adhesion and downstream signaling of adjacent cells in different tissues. One of these molecules, N-cadherin, was first
* Mahboobeh Eslami [email protected] * Younes Ghasemi [email protected] 1
Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
2
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3
Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
4
Recombinant Protein Lab, School of Advanced Medical Sciences and Technologies, Shiraz, Iran
5
Molecular Medicine Department, School of Advanced Medical Sciences and Technology, Shiraz University of Medical Sciences, Shiraz, Iran
6
Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
identified in the brain and then found in different tissues as well as various types of tumors [1–4]. N-cadherin is a transmembrane glycoprotein. It involves in the cell-cell attachment via Ca2+ ions and its extracellular domain, which is folded into five sub-domains, EC1-EC5. It forms homophilic bonds and triggers signaling through the interaction of a cytoplasmic domain that regulates cell-cell adhesion remodeling, cell survival, and migration [5, 6]. The most extreme region of N-cadherin, EC1, contains His-Ala-Val (HAV) and Trp2 sequences, which are indispensable for the homophilic attachment of N-ca
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