We describe new methods for predicting protein tertiary structures to low resolution given the specification of secondary structure and a limited set of long-range NMR distance constraints. The NMR data sets are derived from a realistic protocol involving completely deuterated 15N and 13C-labeled samples. A global optimization method, based upon a modification of the alphaBB (branch and bound) algorithm of Floudas and co-workers, is employed to minimize an objective function combining the NMR distance restraints with a residue-based protein folding potential containing hydrophobicity, excluded volume, and van der Waals interactions. To assess the efficacy of the new methodology, results are compared with benchmark calculations performed via the X-PLOR program of Brünger and co-workers using standard distance geometry/molecular dynamics (DGMD) calculations. Seven mixed alpha/beta proteins are examined, up to a size of 183 residues, which our methods are able to treat with a relatively modest computational effort, considering the size of the conformational space. In all cases, our new approach provides substantial improvement in root-mean-square deviation from the native structure over the DGMD results; in many cases, the DGMD results are qualitatively in error, whereas the new method uniformly produces high quality low-resolution structures. The DGMD structures, for example, are systematically non-compact, which probably results from the lack of a hydrophobic term in the X-PLOR energy function. These results are highly encouraging as to the possibility of developing computational/NMR protocols for accelerating structure determination in larger proteins, where data sets are often underconstrained.
Al NMR: a novel NMR data processing program optimized for sparse sampling
Al NMR: a novel NMR data processing program optimized for sparse sampling
Abstract Sparse sampling in biomolecular multidimensional NMR offers increased acquisition speed and resolution and, if appropriate conditions are met, an increase in sensitivity. Sparse sampling of indirectly detected time domains combined with the direct truly multidimensional Fourier transform has elicited particular attention because of the ability to generate a final spectrum amenable to traditional analysis techniques. A number of sparse sampling schemes have been described including radial sampling, random...
nmrlearner
Journal club
0
11-17-2011 01:47 AM
[NMR paper] Application of sparse NMR restraints to large-scale protein structure prediction.
Application of sparse NMR restraints to large-scale protein structure prediction.
Related Articles Application of sparse NMR restraints to large-scale protein structure prediction.
Biophys J. 2004 Aug;87(2):1241-8
Authors: Li W, Zhang Y, Skolnick J
The protein structure prediction algorithm TOUCHSTONEX that uses sparse distance restraints derived from NMR nuclear Overhauser enhancement (NOE) data to predict protein structures at low-to-medium resolution was evaluated as follows: First, a representative benchmark set of the Protein Data Bank...
nmrlearner
Journal club
0
11-24-2010 10:01 PM
[NMR paper] CORCEMA refinement of the bound ligand conformation within the protein binding pocket
CORCEMA refinement of the bound ligand conformation within the protein binding pocket in reversibly forming weak complexes using STD-NMR intensities.
Related Articles CORCEMA refinement of the bound ligand conformation within the protein binding pocket in reversibly forming weak complexes using STD-NMR intensities.
J Magn Reson. 2004 May;168(1):36-45
Authors: Jayalakshmi V, Rama Krishna N
We describe an intensity-restrained optimization procedure for refining approximate structures of ligands within the protein binding pockets using STD-NMR...
nmrlearner
Journal club
0
11-24-2010 09:51 PM
[NMR paper] TOUCHSTONEX: protein structure prediction with sparse NMR data.
TOUCHSTONEX: protein structure prediction with sparse NMR data.
Related Articles TOUCHSTONEX: protein structure prediction with sparse NMR data.
Proteins. 2003 Nov 1;53(2):290-306
Authors: Li W, Zhang Y, Kihara D, Huang YJ, Zheng D, Montelione GT, Kolinski A, Skolnick J
TOUCHSTONEX, a new method for folding proteins that uses a small number of long-range contact restraints derived from NMR experimental NOE (nuclear Overhauser enhancement) data, is described. The method employs a new lattice-based, reduced model of proteins that explicitly...
nmrlearner
Journal club
0
11-24-2010 09:16 PM
[NMR paper] An efficient branch-and-bound algorithm for the assignment of protein backbone NMR pe
An efficient branch-and-bound algorithm for the assignment of protein backbone NMR peaks.
Related Articles An efficient branch-and-bound algorithm for the assignment of protein backbone NMR peaks.
Proc IEEE Comput Soc Bioinform Conf. 2002;1:165-74
Authors: Lin G, Xu D, Chen ZZ, Jiang T, Wen J, Xu Y
NMR resonance assignment is one of the key steps in solving an NMR protein structure. The assignment process links resonance peaks to individual residues of the target protein sequence, providing the prerequisite for establishing intra- and...
nmrlearner
Journal club
0
11-24-2010 08:49 PM
[NMR paper] De novo protein structure determination using sparse NMR data.
De novo protein structure determination using sparse NMR data.
Related Articles De novo protein structure determination using sparse NMR data.
J Biomol NMR. 2000 Dec;18(4):311-8
Authors: Bowers PM, Strauss CE, Baker D
We describe a method for generating moderate to high-resolution protein structures using limited NMR data combined with the ab initio protein structure prediction method Rosetta. Peptide fragments are selected from proteins of known structure based on sequence similarity and consistency with chemical shift and NOE data. Models...
nmrlearner
Journal club
0
11-19-2010 08:29 PM
[NMR paper] Structure refinement of the glucocorticoid receptor-DNA binding domain from NMR data
Structure refinement of the glucocorticoid receptor-DNA binding domain from NMR data by relaxation matrix calculations.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles Structure refinement of the glucocorticoid receptor-DNA binding domain from NMR data by relaxation matrix calculations.
J Mol Biol. 1995 Apr 7;247(4):689-700
Authors: van Tilborg MA, Bonvin AM, Hård K, Davis AL, Maler B, Boelens R, Yamamoto KR, Kaptein R
The solution structure of the glucocorticoid...
nmrlearner
Journal club
0
08-22-2010 03:41 AM
[NMR paper] Refinement of the NMR structures for acyl carrier protein with scalar coupling data.
Refinement of the NMR structures for acyl carrier protein with scalar coupling data.
Related Articles Refinement of the NMR structures for acyl carrier protein with scalar coupling data.
Proteins. 1990;8(4):377-85
Authors: Kim Y, Prestegard JH
Structure determination of small proteins using NMR data is most commonly pursued by combining NOE derived distance constraints with inherent constraints based on chemical bonding. Ideally, one would make use of a variety of experimental observations, not just distance constraints. Here, coupling...
A branch and bound algorithm for protein structure refinement from sparse NMR data se
Linear Mode
