Rational drug repurposing for cancer by inclusion of the unbiased molecular dynamics simulation in the structure-based virtual screening approach: Challenges and breakthroughs

Managing cancer is now one of the biggest concerns of health organizations. Many strategies have been developed in drug discovery pipelines to help rectify this problem and two of the best ones are drug repurposing and computational methods. The combination of these approaches can have immense impact on the course of drug discovery. In silico drug repurposing can significantly reduce the time, the cost and the effort of drug development. Computational methods such as structure-based drug design (SBDD) and virtual screening can predict the potentials of small molecule binders, such as drugs, for having favorable effect on a particular molecular target. However, the demand for accuracy and efficiency of SBDD requires more sophisticated and complicated approaches such as unbiased molecular dynamics (UMD) simulation that has been recently introduced. As a complementary strategy, the knowledge acquired from UMD simulations can increase the chance of finding the right candidates and the pipeline of its administration is introduced and discussed in this review. An elaboration of this pipeline is also made by detailing an example, the binding and unbinding pathways of dasatinib-c-Src kinase complex, which shows that how influential this method can be in rational drug repurposing in cancer treatment.