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Lecture Nigel G.J. Richards


17 June 2005 FWN-Building 5116.0116, Nijenborgh 4, 9747 AG, Groningen
Speaker: Dr. Nigel G.J. Richards
Affiliation: Department of Chemistry, University of Florida, Gainesville, FL, USA
Title: Hybrid DFT and other computational methods in modeling transition metal-dependent enzymes: recent studies of the Fe(III) center in nitrile hydratase
Date: Fri Jun 17, 2005
Start: 11.00
Location: FWN-Building 5116.0116
Host: R. Broer
Telephone: +31 50 363 4374


The role of metalloenzyme structure in modulating transition metal reactivity is often difficult to assess using experimental approaches. For example, the structural features of the protein that underpin the low-spin preference of the non-heme Fe(III) in nitrile hydratase (NHase), and the importance of this spin-state to the catalytic mechanism, are unlikely to be determined by site-directed mutagenesis and/or characterization of model Fe(III) complexes. Density functional theory (DFT) calculations represent a method for determining the electronic structure of metal centers in enzymes, investigating the properties of hypothetical intermediates in the reaction mechanism, and probing the importance of specific protein residues in controlling metal chemistry. The application of DFT calculations to the study of open-shell systems is, however, fraught with difficulties in both the technical aspects of performing such calculations and the interpretation of results. In this lecture, we will discuss computational studies that have not only revealed the importance of post-translational modifications in the regulation of nitrile hydratase by nitric oxide (NO) but also provided unique insights into the electronic properties of the Fe(III) center in the enzyme. In addition, a series of ligand exchange and pKa calculations will be reported that raise new questions concerning the hypothetical mechanisms of the enzyme-catalyzed hydration reaction.
Last modified:22 October 2012 2.30 p.m.