Molecular dynamic simulations and QM/MM studies addressed to build an active Tryptophan Synthase model. A critical enzyme to treat tuberculosis

The latest data from the World Health Organization (WHO) underline the urgent need for the validation of new targets against tuberculosis (TB). Tryptophan Synthase (TSase) has been pointed has a good candidate, but its allosteric particularities turn it into a challenge both for experimentalists and for computational biochemists. In this study, molecular dynamic simulations and QM/MM studies were performed to build a closed conformation of a TSase model containing the substrate Indole-3-glycerolphosphate (IGP) in the α-active site and the PLP in its external aldimine form in the β-active site. The results have shown that there is a conserved water molecule in the α-active site of the enzyme that should be important for the catalytic process. The built model is stable and can be the basis for further studies.