Computer Aided Drug Design of 1,2,3-Triazole Fused Bioactive Derivative Targeting Glucosamine-6-Phosphate Synthase (GlmS) – XRD, Computational Crystallography, and Molecular Simulation Approach

Abstract

The crystal structure of a 1,2,3-triazole fused heterocyclic derivative 2-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(2,4-dichlorophenyl)-6-phenyl pyridine (DICLPY; 4h) is reported. The structural characterization is done by single crystal X-ray technique. The Hirshfeld surfaces (HS) and 2D fingerprint graphs are generated to investigate the inter atomic contacts contribution for structure by CrystalExplorer 17.5 program. The pairwise interaction energies between neighboring molecules are computed at the B3LYP/6-31G(d,p) method. This interaction energy analysis showed that the total stability of the DICLPY structure is mainly contributed by the dispersion force factor followed by the coulomb potential force factor. The DFT-based HOMO, LUMO orbitals and molecular electrostatic potential map are studied to identify the reactivity of our molecule. In-silico molecular docking technique is used to inspect the DICLPY compound as a possible antibacterial agent by docking with Glucosamine-6-phosphate synthase protein (PDB ID: 2VF5) using PyRx and AutoDock Vina programs. The molecular dynamics simulation is performed to examine the physical movement of our molecule DICLPY with Glucosamine-6-phosphate synthase protein for 100 ns time period. MD simulation revealed the greater stability of DICLPY and Glucosamine-6-phosphate synthase protein complex during the simulation period.

Keywords:

• Drug design
• Hirshfeld surface
• interaction energy calculation
• molecular docking
• molecular dynamics

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Disclosure statement

No potential conflict of interest was reported by the authors.

Authors' contributions

RaviKumar Chandrasekaran: Conceptualization, Methodology, Software Validation, Supervision, Investigation, Writing - Original draft preparation.

T. Silambarasan: Data curation, Visualization, Software Validation.

RaviKumar Chandrasekaran & S. Murugavel: Writing-Reviewing and Editing, Formal analysis, Resources.