On the Effect of Varying Constraints in the Quantum Mechanics Only Modeling of Enzymatic Reactions: The Case of Acetylene Hydratase

ABSTRACT: Quantum mechanics only (QM-only) studies of enzymatic reactions employ a coordinate-locking scheme, in which certain key atoms at the periphery of the chosen cluster model are fixed to their crystal structure positions. We report a case study on acetylene hydratase to assess the uncertainties introduced by this scheme. Random displacements of 0.1, 0.15, and 0.2 Å were applied at the ten terminal atoms fixed in the chosen 116-atom cluster model to generate sets of ten distorted structures for each given displacement. The relevant stationary points were reoptimized under these modified constraints to determine the variations of the computed energies and geometries induced by the displacements of the fixed atoms. Displacements of 0.1 Å cause a relatively minor perturbation that can be accommodated during geometry optimization, resulting in rather small changes in key bond distances and relative energies (typically of the order of 0.01 Å and 1 kcal/mol), whereas displacements of 0.2 Å lead to larger fluctuations (typically twice as high) and may sometimes even cause convergence to different local minima during geometry optimization. A literature survey indicates that protein crystal structures with a resolution higher than 2.0 Å are normally associated with a coordinate error of less than 0.1 Å for the backbone atoms