Despite the recent advancements in computational power, and in the theoretical approaches, obtaining reliable QM(ab-initio)/MM free energy results in condensed phase remain highly challenging. To this end, our recently proposed paradynamics (PD) approach (Nikolay V. Plotnikov and Arieh Warshel, J. Phys. Chem. B. 2012, 116, 10342-10356), to carry out the QM/MM free energy calculations in condensed phases, appears to be very promising and computationally tractable. In order to establish the reliability and the applicability of the PD approach, we estimated the activation free energy barriers associated with the proton transfer pathways (direct vs second water mediated) in the hydrated metaphosphate, which is used as a representative model for the intermediate state along the minimum free energy pathway corresponding to the free energy surface of the phosphate monoester hydrolysis in aqueous solution. The results obtained are quite encouraging and are in very good agreement with the corresponding estimates obtained recently using other QM(ai)/MM approaches (Nikolay V. Plotnikov et al. J. Phys. Chem. B. 2013, 117, 12807-128019). We are now exploring the molecular origin of the activation of GTPase in RasGap using the PD approach.

Molecular origin of the activation of GTPase: Paradynamics (PD) study

248th National Meeting (2014)

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