The principal goals of this project are the development of algorithms that allow one to make the best use of NMR data to determine solution structures of biomolecules, to assess in a systematic fashion their accuracy and precision, and to explore the extent to which dynamical information can be extracted from NMR data. This will involve the following components: Studies of conformation-dependent chemical shifts and anisotropies. Ab initio quantum chemistry and empirical calculations will be used to explore patterns of shift anisotropies in peptide and nucleic acid fragments. An initial emphasis will be on 31P anisotropies in nucleic acids and 13CO anisotropies in proteins. Updated refinement methods. Refinement models will be deveoped that use generalized Born solvation models, and which incorporate conformational disorder through the """"""""locally enhanced sampling"""""""" model that uses multiple copies of portions of the macromolecule. Studies on protein and nucleic acid dynamics. Long-time scale molecular dynamics simulations (initially on binase and ribonuclease H) will be used to model NMR relaxaxtion, with attention paid to anisotropic tumbling, to the correlation between internal and overall motions, and to conformational disorder. This will include an analysis of contributions from internal motions to chemical shift anisotropy (CSA) relaxation and to CSA-dipolar cross-correlated relaxation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM045811-13
Application #
6615016
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Wehrle, Janna P
Project Start
1991-04-01
Project End
2007-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
13
Fiscal Year
2003
Total Cost
$281,550
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Hoop, Cody L; Zhu, Jie; Nunes, Ana Monica et al. (2017) Revealing Accessibility of Cryptic Protein Binding Sites within the Functional Collagen Fibril. Biomolecules 7:
Shirts, Michael R; Klein, Christoph; Swails, Jason M et al. (2017) Lessons learned from comparing molecular dynamics engines on the SAMPL5 dataset. J Comput Aided Mol Des 31:147-161
Debiec, Karl T; Cerutti, David S; Baker, Lewis R et al. (2016) Further along the Road Less Traveled: AMBER ff15ipq, an Original Protein Force Field Built on a Self-Consistent Physical Model. J Chem Theory Comput 12:3926-47
Hsu, Che-Hsiung; Park, Sangho; Mortenson, David E et al. (2016) The Dependence of Carbohydrate-Aromatic Interaction Strengths on the Structure of the Carbohydrate. J Am Chem Soc 138:7636-48
Fu, Iwen; Case, David A; Baum, Jean (2015) Dynamic Water-Mediated Hydrogen Bonding in a Collagen Model Peptide. Biochemistry 54:6029-37
Giamba?u, George M; Gebala, Magdalena K; Panteva, Maria T et al. (2015) Competitive interaction of monovalent cations with DNA from 3D-RISM. Nucleic Acids Res 43:8405-15
Gutmanas, Aleksandras; Adams, Paul D; Bardiaux, Benjamin et al. (2015) NMR Exchange Format: a unified and open standard for representation of NMR restraint data. Nat Struct Mol Biol 22:433-4
Swails, Jason; Zhu, Tong; He, Xiao et al. (2015) AFNMR: automated fragmentation quantum mechanical calculation of NMR chemical shifts for biomolecules. J Biomol NMR 63:125-39
Giamba?u, George M; York, Darrin M; Case, David A (2015) Structural fidelity and NMR relaxation analysis in a prototype RNA hairpin. RNA 21:963-74
Salmon, Loïc; Giamba?u, George M; Nikolova, Evgenia N et al. (2015) Modulating RNA Alignment Using Directional Dynamic Kinks: Application in Determining an Atomic-Resolution Ensemble for a Hairpin using NMR Residual Dipolar Couplings. J Am Chem Soc 137:12954-65

Showing the most recent 10 out of 28 publications