Understanding Enzymatic Hydrolysis Mechanisms using Computer Simulations

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The hydrolysis of guanosine triphoshate (GTP) and other nucleotides through specific enzymes plays an important role in many life-giving processes. Despite intense experimental and theoretical research on a range of different such cleaving proteins the mechanism of nucleotide hydrolysis still remains largely unknown. The protein under investigation here is the GTPase “human guanylate binding protein 1” (hGBP1). It was chosen as it exhibits a particularly rich reaction sequence by which its active center hydrolyses GTP first to GDP and finally to GMP in two consecutive steps. This property, amongst others, makes this GTPase an excellent system on which to study such catalytical processes using first principles methods. Therefore the general aim of this project is the detailed elucidation of the reaction mechanisms of both the GTP and GDP hydrolysis steps in hGBP1 making use of state of the art multiscale simulation techniques which allow us to elucidate the mechanisms on the fully atomistic level at ambient conditions in the protein.