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| - Dynamical Flexibility and Proton Transfer in the ArginaseActive Site Probed by ab Initio Molecular Dynamics
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| - We have used ab initio molecular dynamics (AIMD) to investigate the dynamical flexibility of thebridged binuclear structural motif in the active site of arginase. Dynamical transformations play a crucialrole in catalysis. We have provided direct insight into the motions of the first-shell ligands with emphasison the chelating and bridging carboxylates. In the case of the terminal Asp234 residue we observe changesin the binding mode (carboxylate shifts). AIMD dynamics of sufficient duration has allowed us to observeproton transfer from the bridging nucleophile to the catalytically essential Asp 128 residue and to map theunderlying free energy surface in terms of simple reaction coordinates, such as the oxygen−oxygen distanceRo-o and the asymmetric stretch δ. This has provided valuable insight into the nature of the last step of thecatalytic cycle. In addition, constrained molecular dynamics permitted us to compare the deprotonationfree energy of the bridging nucleophile in the case of native versus metal-depleted arginase.
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