High throughput screening, docking, and molecular dynamics studies to identify potential inhibitors of human calcium/calmodulin-dependent protein kinase IV

Beg, Anam; Khan, Faez I; Lobb, Kevin A; Islam, Asimul; Ahmad, Faizan; Hassan, M Imtaiyaz

Title: High throughput screening, docking, and molecular dynamics studies to identify potential inhibitors of human calcium/calmodulin-dependent protein kinase IV
Creator: Beg, Anam
Creator: Khan, Faez I
Creator: Lobb, Kevin A
Creator: Islam, Asimul
Creator: Ahmad, Faizan
Creator: Hassan, M Imtaiyaz
Subject: To be catalogued
Date Issued: 2019
Date: 2019
Type: text
Type: article
Identifier: http://hdl.handle.net/${Handle}
Identifier: vital:74587
Identifier: xlink:href="https://doi.org/10.1080/07391102.2018.1479310"
Description: Calcium/calmodulin-dependent protein kinase IV (CAMKIV) is associated with many diseases including cancer and neurodegenerative disorders and thus being considered as a potential drug target. Here, we have employed the knowledge of three-dimensional structure of CAMKIV to identify new inhibitors for possible therapeutic intervention. We have employed virtual high throughput screening of 12,500 natural compounds of Zinc database to screen the best possible inhibitors of CAMKIV. Subsequently, 40 compounds which showed significant docking scores (−11.6 to −10.0 kcal/mol) were selected and further filtered through Lipinski rule and drug likeness parameter to get best inhibitors of CAMKIV. Docking results are indicating that ligands are binding to the hydrophobic cavity of the kinase domain of CAMKIV and forming a significant number of non-covalent interactions. Four compounds, ZINC02098378, ZINC12866674, ZINC04293413, and ZINC13403020, showing excellent binding affinity and drug likeness were subjected to molecular dynamics simulation to evaluate their mechanism of interaction and stability of protein-ligand complex. Our observations clearly suggesting that these selected ligands may be further employed for therapeutic intervention to address CAMKIV associated diseases.
Format: computer
Format: online resource
Format: application/pdf
Format: 1 online resource (14 pages)
Format: pdf
Publisher: Taylor and Francis
Language: English
Relation: Journal of Biomolecular Structure and Dynamics
Relation: Beg, A., Khan, F.I., Lobb, K.A., Islam, A., Ahmad, F. and Hassan, M.I., 2019. High throughput screening, docking, and molecular dynamics studies to identify potential inhibitors of human calcium/calmodulin-dependent protein kinase IV. Journal of Biomolecular Structure and Dynamics, 37(8), pp.2179-2192
Relation: Journal of Biomolecular Structure and Dynamics volume 37 number 8 p. 2179 2019 1538-0254
Rights: Publisher
Rights: Use of this resource is governed by the terms and conditions of the Taylor and Francis Online Terms and Conditions Statement (https://www.tandfonline.com/terms-and-conditions)
Rights: Closed Access

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