Search for conformation of thiosemicarbazone reagents and their complexes with metals by using Monte Carlo and docking simulation


thiosemicarbazone reagent
Monte Carlo simulation
PM3 and MM calculation

How to Cite

Quang NM, Mau TX, Han PNN, Tat PV. Search for conformation of thiosemicarbazone reagents and their complexes with metals by using Monte Carlo and docking simulation. hueuni-jns [Internet]. 2020Jul.10 [cited 2024Jun.22];129(1D):51-9. Available from:


In this study, the conformation of ML2 complexes of new thiosemicarbazone reagents with metal cations Cd2+, Ni2+, Cu2+, Hg2+, Pb2+, Mn2+, and Zn2+ is investigated. The methods include MM+ and PM3 calculations with the Monte Carlo techniques using the Metropolis algorithm in the temperature range of 298–473 K. The initial selection conformation was carried out randomly after 15 repeated conformations, and 30 conformations were rejected. The conformations were chosen to change by changing the torsional-dihedral angles at the position of the metal cation associated with the donor atoms N and S of the thiosemicarbazone reagents. This was performed by randomly changing the dihedral angles to create new structures, and then the energy values of these angles were minimized with the PM3 and MM+ calculation. The lowest suitable energies were accumulated, while high- or duplicate-energy structures were discarded. The docking method was also employed to screen the most suitable metal-thiosemicarbazone complexes that bind to the active site on the SARS-CoV-2 protein. The docking method enabled us to choose the molecular conformation of the most significant Cd2+-thiosemicarbazone complex.


  1. Howard E, Kollman PA. An analysis of current methodologies for conformational searching of complex molecules. Journal of Medicinal Chemistry. 1988;31(9):1669-1675.
  2. Kolossváry I, Guida WC. Torsional flexing: Conformational searching of cyclic molecules in biased internal coordinate space. 1993;14(6):691-698.
  3. Kumar S, Dhar DN, Saxena PN. Applications of metal complexes of Schiff bases-A review. Journal of Scientific and Industrial Research. 2009;68(3):181-187.
  4. Khan T, Ahmad R, Joshi S, Khan AR. Anticancer potential of metal thiosemicarbazone complexes: A review. Der Chemica Sinica. 2015;6(12):1-11.
  5. Aljahdali M, El-Sherif AA. Synthesis, characterization, molecular modeling and biological activity of mixed ligand complexes of Cu(II), Ni(II) and Co(II) based on 1,10-phenanthroline and novel thiosemicarbazone. Inorganica Chimica Acta. 2013; 407:58-68.
  6. HyperChemTM. Version 7.5. Florida, USA: Hypercube Inc; 2002.
  7. Chang G, Guida WC, Still WC. An Internal Coordinate Monte Carlo Method for Searching Conformational Space. Journal of the American Chemical Society. 1989;111(12):4379-4386.
  8. Hypercube. HyperChemTM Computational Chemistry: Part 1. Practical Guide, Part 2. Theory and Methods. Canada: Hypercube Inc; 1996.
  9. Sherman W, Day T, Jacobson MP, Friesner RA, Farid R. Novel procedure for modeling ligand/receptor induced fit effects. Journal of Medicinal Chemistry. 2006 01;49(2):534-553.
  10. Subramanian J, Sharma S, B-Rao C. Modeling and selection of flexible proteins for structure-based drug design: backbone and side chain movements in p38 MAPK. ChemMedChem. 2008;3(2):36-44.
  11. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARSCoV-2 and other lineage B betacoronaviruses. Nature Microbiology. 2020;5(4):562-569.
  12. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. New England Journal of Medicine. 2020;382(8):727-733.
  13. Thuy BTP, My TTA, Hai NTT, Hieu LT, Hoa TT, Loan HTP, et al. Investigation into SARS-CoV‑2 resistance of compounds in garlic essential oil. ACS Omega. 2020;5(14):8312-8320.
  14. My TTA, Loan HTP, Hai NTT, Hieu LT, Hoa TT, Thuy BTP, et al. Evaluation of the inhibitory activities of COVID-19 of melaleuca cajuputi oil using docking simulation. ChemistrySelect. 2020; 5(21):6312-6320.
  15. My TTA, Hieu LT, Hai NTT, Loan HTP, Bui TQ, Thuy BTP, et al. Study on SARS-CoV-2 inhibition of some potential drugs using molecular docking simulation. Vietnamese Journal of Chemistry. 2020;58(5):666-674.
  16. Chan JF, Yuan S, Kok K, To KK, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. 2020;395(10223):514-523.
  17. Quang NM, Mau TX, Nhung NTA, An TNM, Tat PV. Novel QSPR modeling of stability constants of metal-thiosemicarbazone complexes by hybrid multivariate technique: GA-MLR, GA-SVR and GA-ANN. Journal of Molecular Structure. 2019;1195:95-109.
  18. An TNM, Phuong PT, Quang NM, Son NV, Cuong NV, Tan LV, et al. Synthesis, Docking Study, Cytotoxicity, Antioxidant, and Anti-microbial Activities of Novel 2,4-Disubstituted Thiazoles Based on Phenothiazine. Current Organic Synthesis. 2020;17(2):151-159.
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