? The aim of this project is to develop a set of computational tools for neutron protein crystallography. At the start of the funding period we will focus on providing tools that can be immediately applied to address the computational bottleneck in neutron protein crystallography and to determine the neutron structures of a series of proteins, many with high biomedical importance that span a spectrum of size and complexity. The ultimate aim is to adapt these computational tools for incorporation into PHENIX (Python-based Hierarchical EnviroNment for Integrated Xtallography) for automated macromolecular crystallography as extensible C++ modules and databases. The software will use and contribute towards basic programming tools for X-ray crystallography in the Computational Crystallography Toolbox (cctbx). Our vision is to contribute to a computational workbench that structural biologists, with a range of crystallographic experience, can use alternatively for neutron or X-ray protein crystallography. The computational tools will integrate all tasks required for neutron intensity data scaling, merging, wavelength normalization, attenuation correction and handling, computation of phases, map generation and interpretation, model building and refinement into one system. Automatic decision making concepts will minimize human interventions and decrease the time needed to refine structures. Software will be generalizable to X-ray protein crystallography. The structure refinement tools will allow global refinement of protein structures against any combination of neutron, X-ray and energy minimization functions. Structural biologists will use the same system in an interoperable way for X-ray, neutron or joined X-ray and neutron analyses. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
6R01GM071939-03
Application #
7277448
Study Section
Special Emphasis Panel (ZRG1-BDMA (01))
Program Officer
Edmonds, Charles G
Project Start
2004-09-08
Project End
2009-08-31
Budget Start
2006-06-01
Budget End
2006-08-31
Support Year
3
Fiscal Year
2005
Total Cost
$101,815
Indirect Cost
Name
Los Alamos National Lab
Department
Type
DUNS #
175252894
City
Los Alamos
State
NM
Country
United States
Zip Code
87545
Dajnowicz, Steven; Seaver, Sean; Hanson, B Leif et al. (2016) Visualizing the Bohr effect in hemoglobin: neutron structure of equine cyanomethemoglobin in the R state and comparison with human deoxyhemoglobin in the T state. Acta Crystallogr D Struct Biol 72:892-903
Das, Amit; Gerlits, Oksana; Parks, Jerry M et al. (2015) Protein Kinase A Catalytic Subunit Primed for Action: Time-Lapse Crystallography of Michaelis Complex Formation. Structure 23:2331-2340
Wan, Qun; Parks, Jerry M; Hanson, B Leif et al. (2015) Direct determination of protonation states and visualization of hydrogen bonding in a glycoside hydrolase with neutron crystallography. Proc Natl Acad Sci U S A 112:12384-9
Michalczyk, Ryszard; Unkefer, Clifford J; Bacik, John-Paul et al. (2015) Joint neutron crystallographic and NMR solution studies of Tyr residue ionization and hydrogen bonding: Implications for enzyme-mediated proton transfer. Proc Natl Acad Sci U S A 112:5673-8
Gerlits, Oksana; Tian, Jianhui; Das, Amit et al. (2015) Phosphoryl Transfer Reaction Snapshots in Crystals: INSIGHTS INTO THE MECHANISM OF PROTEIN KINASE A CATALYTIC SUBUNIT. J Biol Chem 290:15538-48
Gerlits, Oksana; Das, Amit; Keshwani, Malik M et al. (2014) Metal-free cAMP-dependent protein kinase can catalyze phosphoryl transfer. Biochemistry 53:3179-86
Wan, Qun; Zhang, Qiu; Hamilton-Brehm, Scott et al. (2014) X-ray crystallographic studies of family 11 xylanase Michaelis and product complexes: implications for the catalytic mechanism. Acta Crystallogr D Biol Crystallogr 70:11-23
Wan, Qun; Kovalevsky, Andrey Y; Wilson, Mark A et al. (2014) Preliminary joint X-ray and neutron protein crystallographic studies of ecDHFR complexed with folate and NADP+. Acta Crystallogr F Struct Biol Commun 70:814-8
Wan, Qun; Bennett, Brad C; Wilson, Mark A et al. (2014) Toward resolving the catalytic mechanism of dihydrofolate reductase using neutron and ultrahigh-resolution X-ray crystallography. Proc Natl Acad Sci U S A 111:18225-30
Gerlits, Oksana; Waltman, Mary Jo; Taylor, Susan et al. (2013) Insights into the phosphoryl transfer catalyzed by cAMP-dependent protein kinase: an X-ray crystallographic study of complexes with various metals and peptide substrate SP20. Biochemistry 52:3721-7

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