Modelli biofisici in silico per la predizione di inibitori enzimatici in modelli batterici

The development of new drugs is a hard and expensive goal for industry and scientists. The computational approach can drive this process reducing time and costs. This work show pipeline and software to models the interaction between a target enzyme and a small molecule (inhibitor). Usually, allosteric compounds can interact with the protein, inducing conformational rearrangement that affects the functionality of the enzyme. Here the 3D model of one enzyme, the isocitrate lyase (ICL), was modeled starting from a sequence of ICL of Streptomyces coelilolor and, using online tools, allosteric pockets were identified. Finally, the potential Inhibitors were screened using a docking method. ICL is an important factor of virulence and persistence in Mycobacterium tuberculosis, and one commercially available drug was identified: rapamycin, an mTOR inhibitor used in prevention of transplant rejection.