Bioinformatics Analysis of Protein-Inhibitor Interactions for BRAF
DOI:
https://doi.org/10.58445/rars.2749Keywords:
Bioinformatics, Protein, Cancer, Mutations, Comparison StudyAbstract
In this study, Vemurafenib, Encorafenib, and Dabrafenib’s binding affinities were tested. These are all drugs used to inhibit mutated BRAF proteins, which is known to cause several types of cancer. Vemurafenib is usually used to inhibit BRAF V600E (the mutated form of the protein) when presented as melanoma while the other two drugs are used in addition to MEK inhibitors. The computational methods used were primarily docking because molecular docking allows comparisons between the different binding interactions between the drugs and to see which drugs have a higher binding affinity (Journal of Chemical Information and Modeling. (n.d.)). It also identifies which compounds have strong interactions with each other. Both the wild type and the mutant form of BRAF were tested against the three drugs above. Dabrafenib was used as a control against the other two because of how (compared to the other two drugs) it is a well-established and effective targeted therapy. Encorafenib had the lowest free energy for both wild type and mutant BRAF compared to any of the other drugs, and it was also the sole drug where the mutant form had a lower free energy compared to the wild type). Vemurafenib had the highest free energy for both its mutant and its wild type form . The genetic sequence pulled from ClusterOmega is an area of BRAF that is close to the binding site, possibly meaning that BRAF may adapt to different environments or have to interact with different partners in different species, or possibly that its specificity is affected by the environment and other regulations that are different for many species.
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