Exploring quantum computational, molecular docking, and molecular dynamics simulation with MMGBSA studies of ethyl-2-amino-4-methyl thiophene-3-carboxylate

Abstract

2-aminothiophenes derivative, Ethyl-2-amino-4-methyl thiophene-3-carboxylate (EAMC) has been synthesized, characterized, and investigated quantum chemically. It was experimentally investigated by different spectroscopic methods like- NMR (¹H-NMR and ¹³C-NMR), FT-IR, and UV-Visible. B3LYP method and 6-311++G(d,p) basis set were employed for optimization of molecular structure and calculation of wave numbers of normal modes of vibrations and various other important parameters. Calculated bond lengths and angles were compared with the experimental bond lengths and Bond Angle Parameters. Optimized bond parameters and experimental bond parameters were found in good agreement. Complete potential energy distribution assignments were done successfully by VEDA. The HOMO/LUMO energy gap emphasizes adequate charge transfer happening within the molecule. A study of donor-acceptor interconnections was done via NBO analysis. MEP surface analysis was done to demonstrate charge distribution and reactive areas qualitatively in the molecule. The degree of relative localization of electrons was analyzed via ELF Diagram. The Fukui function analysis showed possible sites for attacks by different substituents. By using the TD-DFT method and PCM solvent model, the UV–Vis spectrum (gas, methanol, DMSO) and the maximum absorption wavelength was computed and compared with experimental data. 3D and 2D intermolecular interactions in the crystal were analyzed via Hirshfeld surface analysis and fingerprint plots reveal that the EAMC crystal was stabilized by H–-H/H–-H/C–-H bond formation. The molecular docking was done with 7 different protein receptors on the molecule to find the best ligand-protein interactions. Molecular dynamic simulations and MMGBSA calculations were also carried out to find out the best binding of the ligand with the protein.

Communicated by Ramaswamy H. Sarma

Keywords:

• DFT
• NBO
• docking
• Hirshfeld analysis
• ELF
• NLO

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We acknowledge Dr. B. R. Ambedkar University, Agra, India for providing necessary facilities, CIF- Jiwaji University, Gwalior for recording FT-IR and UV-Vis spectra, IIITM, Jammu for recording NMR spectrum, UGC New Delhi for financial support.