title: Rapid calculation of protein chemical shifts using bond polarization theory and its application to protein structure refinement.
abstract: Although difficult to analyze, NMR chemical shifts provide detailed information on protein structure. We have adapted the semi-empirical bond polarization theory (BPT) to protein chemical shift calculation and chemical shift driven protein structure refinement. A new parameterization for BPT amide nitrogen chemical shift calculation has been derived from MP2 ab initio calculations and successfully evaluated using crystalline tripeptides. We computed the chemical shifts of the small globular protein ubiquitin, demonstrating that BPT calculations can match the results obtained at the DFT level of theory at very low computational cost. In addition to the calculation of chemical shift tensors, BPT allows the calculation of chemical shift gradients and consequently chemical shift driven geometry optimizations. We applied chemical shift driven protein structure refinement to the conformational analysis of a set of Trypanosoma brucei (the causative agent of African sleeping sickness) tryparedoxin peroxidase Px III structures. We found that the interaction of Px III with its reaction partner Tpx seems to be governed by conformational selection rather than by induced fit.
authors.affiliation: Institute for Biological Interfaces, Karlsruhe Institute of Technology, POB 3640, 76021 Karlsruhe, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Jakovkin
authors.forename: Marco
authors.initials: M
authors.lastname: Klipfel
authors.forename: Claudia
authors.initials: C
authors.lastname: Muhle-Goll
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.forename: Burkhard
authors.initials: B
authors.lastname: Luy
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sternberg
mesh_terms: D000465:Algorithms; D000577:Amides / Q000737:chemistry; D006801:Humans; D056004:Molecular Dynamics Simulation; D009584:Nitrogen / Q000032:analysis; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D009842:Oligopeptides / Q000737:chemistry; D010544:Peroxidases / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D015800:Protozoan Proteins / Q000737:chemistry; D014346:Trypanosoma brucei brucei / Q000737:chemistry / Q000201:enzymology; D014353:Trypanosomiasis, African / Q000469:parasitology; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D000577:Amides; D009842:Oligopeptides; D011506:Proteins; D015800:Protozoan Proteins; D025801:Ubiquitin; D010544:Peroxidases; C110959:tryparedoxin peroxidase; D009584:Nitrogen