Abstract A method for generating protein backbone models from backbone only NMR data is presented, which is based on molecular fragment replacement (MFR). In a first step, the PDB database is mined for homologous peptide fragments using experimental backbone-only data i.e. backbone chemical shifts (CS) and residual dipolar couplings (RDC). Second, this fragment library is refined against the experimental restraints. Finally, the fragments are assembled into a protein backbone fold using a rigid body docking algorithm using the RDCs as restraints. For improved performance, backbone nuclear Overhauser effects (NOEs) may be included at that stage. Compared to previous implementations of MFR-derived structure determination protocols this model-building algorithm offers improved stability and reliability. Furthermore, relative to CS-ROSETTA based methods, it provides faster performance and straightforward implementation with the option to easily include further types of restraints and additional energy terms.
Content Type Journal Article
Category Article
Pages 1-11
DOI 10.1007/s10858-012-9632-7
Authors
Georg Kontaxis, Max F. Perutz Laboratories, Department of Structural and Computational Biology, Centre for Molecular Biology, University of Vienna, Campus Vienna Biocenter 5, 1030 Vienna, Austria
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
J Biomol Screen. 2010 Sep;15(8):978-89
Authors: Kobayashi M, Retra K, Figaroa F, Hollander JG, Ab E, Heetebrij RJ, Irth H, Siegal G
Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing...
nmrlearner
Journal club
0
01-13-2011 12:00 PM
RDC derived protein backbone resonance assignment using fragment assembly
RDC derived protein backbone resonance assignment using fragment assembly
Abstract Experimental residual dipolar couplings (RDCs) in combination with structural models have the potential for accelerating the protein backbone resonance assignment process because RDCs can be measured accurately and interpreted quantitatively. However, this application has been limited due to the need for very high-resolution structural templates. Here, we introduce a new approach to resonance assignment based on optimal agreement between the experimental and calculated RDCs from a structural template that...
nmrlearner
Journal club
0
12-31-2010 08:38 PM
Exploring collagen self-assembly by NMR.
Exploring collagen self-assembly by NMR.
Related Articles Exploring collagen self-assembly by NMR.
Phys Chem Chem Phys. 2010 Sep 28;
Authors: Lisitza N, Huang X, Hatabu H, Patz S
The time-dependence of the NMR signal intensity of collagen type I is representative of protein aggregation. It is pH sensitive and can be related to aggregation mechanism.
nmrlearner
Journal club
0
09-30-2010 06:54 PM
[NMR paper] Structure and dynamics of a protein assembly. 1H-NMR studies of the 36 kDa R6 insulin
Structure and dynamics of a protein assembly. 1H-NMR studies of the 36 kDa R6 insulin hexamer.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles Structure and dynamics of a protein assembly. 1H-NMR studies of the 36 kDa R6 insulin hexamer.
J Mol Biol. 1996 Apr 26;258(1):136-57
Authors: Jacoby E, Hua QX, Stern AS, Frank BH, Weiss MA
The structure and dynamics of the R6 human insulin hexamer are investigated by two- and three-dimensional homonuclear 1H-NMR spectroscopy....
nmrlearner
Journal club
0
08-22-2010 02:27 PM
[NMR paper] Structural and dynamic properties of the Fv fragment and the single-chain Fv fragment
Structural and dynamic properties of the Fv fragment and the single-chain Fv fragment of an antibody in solution investigated by heteronuclear three-dimensional NMR spectroscopy.
Related Articles Structural and dynamic properties of the Fv fragment and the single-chain Fv fragment of an antibody in solution investigated by heteronuclear three-dimensional NMR spectroscopy.
Biochemistry. 1994 Mar 22;33(11):3296-303
Authors: Freund C, Ross A, Plückthun A, Holak TA
Fv fragments, heterodimers of the variable light (VL) and variable heavy chain...
nmrlearner
Journal club
0
08-22-2010 03:33 AM
[NMR paper] Structural and dynamic properties of the Fv fragment and the single-chain Fv fragment
Structural and dynamic properties of the Fv fragment and the single-chain Fv fragment of an antibody in solution investigated by heteronuclear three-dimensional NMR spectroscopy.
Related Articles Structural and dynamic properties of the Fv fragment and the single-chain Fv fragment of an antibody in solution investigated by heteronuclear three-dimensional NMR spectroscopy.
Biochemistry. 1994 Mar 22;33(11):3296-303
Authors: Freund C, Ross A, Plückthun A, Holak TA
Fv fragments, heterodimers of the variable light (VL) and variable heavy chain...
nmrlearner
Journal club
0
08-22-2010 03:33 AM
[CNS Yahoo group] PDBePISA assembly, summary and XML data files available from the Pro
PDBePISA assembly, summary and XML data files available from the Pro
The Protein Data Bank in Europe (PDBe; http://pdbe.org/) is pleased to announce the availability of PISA assembly files, summaries and associated XML
More...
An improved algorithm for MFR fragment assembly
Linear Mode
