Orbital - Vol. 13 No. 4 - July-September 2021
FULL PAPERS

Combined Conceptual-DFT, Quantitative MEP Analysis, and Molecular Docking Study of Benzodiazepine Analogs

Rachida Djebaili
Group of Computational and Pharmaceutical Chemistry, LMCE Laboratory, University Mohamed Khider
Nadjib Melkemi
Group of Computational and Pharmaceutical Chemistry, LMCE Laboratory, University Mohamed Khider
Samir Kenouche
Group of Modeling of Chemical Systems using Quantum Calculations, Applied Chemistry Laboratory (LCA). University M. Khider of Biskra, 07000 Biskra
Ismail Daoud
University Abou-BakrBelkaid-Faculty of Science- Department of Chemistry- Laboratory of Natural Substances and Bioactive (LASNABIO)-Tlemcen-Algeria
Mohammed Bouachrine
1. MCNS Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Morocco. 2. EST Khenifra, Sultan Moulay Slimane University,
Halima Hazhazi
Group of Computational and Pharmaceutical Chemistry, LMCE Laboratory, University Mohamed Khider, 07000Biskra
Toufik Salah
Group of Computational and Pharmaceutical Chemistry, LMCE Laboratory, University Mohamed Khider, 07000Biskra
Published October 5, 2021
Keywords
  • Benzodiazepine; dual descriptor; quantitative MEPanalysis; binding site, GABAA, molecular docking
How to Cite
(1)
Djebaili, R.; Melkemi, N.; Kenouche, S.; Daoud, I.; Bouachrine, M.; Hazhazi, H.; Salah, T. Combined Conceptual-DFT, Quantitative MEP Analysis, and Molecular Docking Study of Benzodiazepine Analogs. Orbital: Electron. J. Chem. 2021, 13, 301-315.

Abstract

In the present work, a combined approach based on conceptual-DFT formalism and molecular docking simulations were performed to investigate the chemical reactivity of six Benzodiazepine analogs. Chemical reactivity descriptors derived from the conceptual DFT were determined and discussed to explain the global and local reactivity of the six studied analogs. Also, long-range interactions were studied using the quantitative analyses of molecular electrostatic potential (MEP) on van der Waals surface to identify the nucleophilic and electrophilic sites. Moreover, a statistical analysis was performed to assess the robustness of atomic charges to the basis set. The results revealed that Hirshfeld population analysis (HPA) was the most efficient for this purpose. Molecular docking simulations were performed to predict the binding affinities of the issued molecules and estimate the binding poses into four binding sites, three of them were recently discovered, located in GABAA receptor.

DOI: http://dx.doi.org/10.17807/orbital.v13i4.1607