Computational analyses of interactions between ALK-5 and bioactive ligands: insights for the design of potential anticancer agents.

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Computational analyses of interactions between ALK-5 and bioactive ligands: insights for the design of potential anticancer agents.

J Biomol Struct Dyn. 2017 Nov 13;:1-30

Authors: Almeida MO, Costa CHS, Gomes GC, Lameira J, Alves CN, Honorio KM

Abstract
Activin Receptor-Like Kinase 5 (ALK-5) is related to some types of cancer, such as breast, lung and pancreas. In this study, we have used molecular docking, molecular dynamics simulations and free energy calculations in order to explore key interactions between ALK-5 and six bioactive ligands with different ranges of biological activity. The motivation of this work is the lack of crystal structure for inhibitor-protein complexes for this set of ligands. The understanding of the molecular structure and the protein-ligand interaction could give support for the development of new drugs against cancer. The results show that the calculated binding free energy using MM-GBSA, MM-PBSA and SIE are correlated with experimental data with r(2) = 0.88, 0.80 and 0.94, respectively, which indicate that the calculated bind free energy is in excellent agreement with experimental data. In addition, the results demonstrate that H bonds with Lys232, Glu245, Tyr249, His283, Asp351 and one structural water molecule play an important role for the inhibition of ALK-5. Overall, we discussed about the main interactions between ALK-5 and six inhibitors that may be used as starting point for designing of new molecules to the cancer treatment.

PMID: 29132261 [PubMed - as supplied by publisher]

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