• MÁRCIA MACHADO MARINHO Department of Clinical and Toxicological Analysis, Federal University of Ceara, Ceara, Brazil.
  • RICARDO PIRES DOS SANTOS Department of Computer Engineering/Biotechnology, Federal University of Ceara, Ceara, Brazil.
  • EVELINE MATIAS BEZERRA Department of Exact and Natural Sciences, Federal Rural University of Semiarid (UFERSA), Mossoró, Rio Grande do Norte, Brazil.
  • RONER FERREIRA COSTA Department of Exact and Natural Sciences, Federal Rural University of Semiarid (UFERSA), Mossoró, Rio Grande do Norte, Brazil.
  • CIRO SIQUEIRA FIGUEIRA Department of Computer Engineering/Biotechnology, Federal University of Ceara, Ceara, Brazil.
  • ALICE MARIA COSTA MARTINS Department of Clinical and Toxicological Analysis, Federal University of Ceara, Ceara, Brazil.
  • PEDRO LIMA NETO Department of Analytical Chemistry and Physical-Chemistry, Federal University of Ceara, Ceara, Brazil.
  • EMMANUEL SILVA MARINHO Dom Aureliano Matos Faculty of Philosophy, Ceara State University, Ceara, Brazil.
  • VALDER NOGUEIRA FREIRE Department of Physics, Federal University of Ceara, Ceara, Brazil.
  • EUDENILSON LINS ALBUQUERQUE Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.


Objective: The objective of this study was to use the molecular fractionation with conjugate caps (MFCC) method to elucidate the possible interaction mechanism of anacardic acid (AA) with the saturated alkyl chain (AA0) in the Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPHD) enzyme.

Methods: Initially, the geometry optimization of the AA three-dimensional structure (with the pentadecyl chain) was performed using density functional theory (B3LYP) calculations. With the AA0 optimization data, it was possible to plot the molecular electrostatic potential (MESP) surface. Molecular docking simulation was performed using automated coupling with the AutoDock Vina program. The best-fit conformation in the docking simulation of AA0 is the binding site used for the construction of the TcGAPHD-AA0 complex. Interaction energies between the AA0 molecule and the amino acid residues of the TcGAPHD enzyme were estimated using the MFCC strategy.

Results: To obtain more reliable quantitative information on the interaction of AA with the active site of the TcGAPHD enzyme, the fragmentation method was combined with conjugated layers (MFCC) and molecular docking. It can be observed that the AA0 molecule occupies a region near the active site of the chalepin molecule in the TcGAPHD enzyme, and the Ile13 residue has the strongest binding energy of approximately 25 kcal/mol with AA0, through a strong Van der Waals interaction.

Conclusion: The paper presents an improved quantitative analysis approach for assessing the contribution of individual amino acids to the free energy of interaction between AA and TcGAPHD. Specifically, the paper illustrates the advantageous approach of combining molecular docking with the MFCC method.

Keywords: Anacardic acid, Chagas disease, Density functional theory, Glyceraldehyde-3-phosphate dehydrogenase, Trypanosoma cruzi, Molecular electrostatic potential, Molecular fractionation with conjugate caps, molecular docking


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