Quantified electrostatic preorganization in enzymes using the geometry of the electron charge density

Abstract

The exact positions of critical points in the charge density in enzyme active sites reflects electrostatic preorganization.

Revealing quantum mechanical effects in enzyme catalysis with large-scale electronic structure simulation

“…Although significant QM region dependence and a mandate for larger QM regions in QM/MM simulation have been noted for numerous properties, 35,[51][52][53][54][55][58][59][60] COMT itself may be a good example of more extreme challenges in QM/MM simulation for enzyme catalysis. The substrates, SAM and CAT, themselves are large at already 64 atoms, and the size of SAM (ca.…”

“…The majority of resulting studies have revealed an exceptionally slow approach to asymptotic limits (ca. 500-1000 atoms) for radial convergence: NMR shieldings, 48,49 proton transfer, 57 solvation effects, 50 barrier heights, 35,51,52 forces, 53 excitation energies, 54,58,59 partial charges, 55 bond critical points, 60 and redox potentials. 56 There are cases where smaller QM regions have been motivated (e.g., in DNA models 61 and the cytochrome P450cam metalloenzyme 62 ), so there is increasing consensus that it is important to determine the extent to which a given property is sensitive to the QM region size.…”

Installation of internal electric fields by non-redox active cations in transition metal complexes

“…The crown moiety appended to the four-coordinate Schiff-base ligand can accommodate a large range of cationic metal centers (M 2 ). Alkali and alkaline earth metals were utilized because they are known to generate signicant electric elds in enzymes 33,34 and zeolite cavities. 35 A signicant shi in the Co(II/I) redox potential was observed upon installation of the redox-inactive cation.…”

Direct Look at the Electric Field in Ketosteroid Isomerase and Its Variants

“…It has been shown that residues in the first and second coordination sphere contribute the most to this electric field. [4][5][6][7] Hence, the protein scaffold needs to be folded in a specific way such that these residues are in the correct spatial position and orientation to optimize the effect of the electric field on the active site.…”