Title:In Silico Screening and Molecular Dynamics Simulations against Tyrosine-protein Kinase Fyn Reveal Potential Novel Therapeutic Candidates for Bovine Papillomatosis
Volume: 31
Issue: 37
Author(s): Gerlane Salgueiro Barros, Débora Machado Barreto, Sandy Gabrielly Souza Cavalcanti, Tiago Branquinho Oliveira, Ricardo Pereira Rodrigues and Marcus Vinicius de Aragão Batista*
Affiliation:
- Laboratory of Molecular Genetics and Biotechnology, Department of Biology, Center for Biological and
Health Sciences, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil
Keywords:
Bovine papillomavirus, virtual screening, Fyn, tyrosine-protein, MDS, papillomatosis.
Abstract:
Background: Decreased beef productivity due to papillomatosis has led to
the development and identification of novel targets and molecules to treat the disease.
Protein kinases are promising targets for the design of numerous chemotherapy drugs.
Objective: This study aimed to screen and design new inhibitors of bovine Fyn, a protein
kinase, using structure-based computational methods, such as molecular docking
and molecular dynamics simulation (MDS).
Methods: To carry out the molecular docking analysis, five ligands obtained through
structural similarity between active compounds along with the cross-inhibition function
between the ChEMBL and Drugbank databases were used. Molecular modeling was performed,
and the generated models were validated using PROCHECK and Verify 3D.
Molecular docking was performed using Autodock Vina. The complexes formed between
Fyn and the three best ligands had their stability assessed by MDS. In these simulations,
the complexes were stabilized for 100 ns in relation to a pressure of 1 atm, with
an average temperature of 300 k and a potential energy of 1,145,336 kJ/m converged in
997 steps.
Results: Docking analyses showed that all selected ligands had a high binding affinity
with Fyn and presented hydrogen bonds at important active sites. MDS results support
the docking results, as the ligand showed similar and stable interactions with amino
acids present at the binding site of the protein. In all simulations, sorafenib obtained the
best results of interaction with the bovine Fyn.
Conclusion: The results highlight the identification of possible bovine Fyn inhibitors;
however, further studies are important to confirm these results experimentally.
