Elucidating the Catalytic Reaction Mechanism of Orotate Phosphoribosyltransferase by Means of X-ray Crystallography and Computational Simulations

Abstract

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How a Second Mg2+ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study

“…This approach has been successfully applied to different enzymatic reactions. 50,75,[79][80][81][82][83][84] Figure 3 shows the choice of the CVs for string method and path CV calculations. CVs 1 and 2 describe the breaking and formation of P-O bonds, respectively, while CVs and 4 represent the proton transfer from the threonine's hydroxyl group to Asp127.…”

Molecular Basis of SARS-CoV-2 Infection and Rational Design of Potential Antiviral Agents: Modeling and Simulation Approaches

“…Indeed, high-throughput molecular simulations, and, in particular, all-atom molecular dynamics (MD), allow us to represent complex phenomena taking place between complex systems at an atomic-scale resolution. They have proven to be extremely efficient in modeling the interactions and the related conformational reorganization between proteins, nucleic acids, and lipid membranes. − Molecular simulations have allowed us to resolve the complex processes related to, among others, enzymatic catalysis − and DNA lesion production and repair − and to unravel the key mechanisms of passive and active membrane transporters. − These successes have also been made possible by the impressive development of computational algorithms, including enhanced sampling and free-energy methods, which nowadays allow us to simulate the behavior of systems of hundreds of thousands of atoms up to the microsecond time scale. , …”

Solvation Induction of Free Energy Barriers of Decarboxylation Reactions in Aqueous Solution from Dual-Level QM/MM Simulations

“…Equation is typically used directly in combined QM/MM calculations, but its efficiency is limited by the cost and unfavorable scaling of high-level QM methods. In fact, it is more convenient to adopt an alternative, equivalent representation by separating the electronic energy for the solute (the first term of eq ) into a constant reference-value ( E X o ) in the gas phase and a net solute–solvent interaction energy. ,, where the second term, Δ H Xs tr = ( H X + H Xs ) – E X o , formally defines the energy of the transfer for solute X from the gas phase into solution, and E X o can be the global energy minimum at a fixed geometry as the reference state (the zero of relative energies) or could be a variable as a function of the reaction coordinate along a minimum-energy path. In the first case, the energy variation is included in Δ H Xs tr , whereas in the second choice, the transfer term corresponds purely to the solute–solvent interaction energy.…”

“…In fact, it is more convenient to adopt an alternative, equivalent representation by separating the electronic energy for the solute (the first term of eq 1) into a constant reference-value (E X o ) in the gas phase and a net solute−solvent interaction energy. 62,64,65…”