A global optimization method for intensity-restrained structure refinement, based on variable target function (VTF) analysis, is illustrated using experimental data on a model peptide, gramicidin-S (GS) dissolved in D...
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A global optimization method for intensity-restrained structure refinement, based on variable target function (VTF) analysis, is illustrated using experimental data on a model peptide, gramicidin-S (GS) dissolved in DMSO. The method (referred to as VARTIGO for variabletarget intensity-restrained global optimization) involves minimization of a targetfunction in which the range of NOE contacts is gradually increased in successive cycles of optimization in dihedral angle space. Several different starting conformations (including all-trans) have been tested to establish the validity of the method. Not all optimizations were successful, but these were readily identifiable from their large NOE R-factors. We also show that it is possible to simultaneously optimize the rotational correlation time along with the dihedral angles. The structural features of GS thus obtained from the successful optimizations are in excellent agreement with the available experimental data. A comparison is made with structures generated from an intensity-restrained single targetfunction (STF) analysis. The results on GS suggest that VARTIGO refinement is capable of yielding better quality structures. Our work also underscores the need for a simultaneous analysis of different NOE R-factors in judging the quality of optimized structures. The NOESY data on GS in DMSO appear to provide evidence for the presence of two orientations for the ornithine side chain, in fast exchange. The NOESY spectra for this case were analyzed using a relaxation-rate matrix which is a weighted average of the relaxation rate matrices for the individual conformations.
The 21-amino acid peptides siamycin II (BMY-29303) and siamycin I (BMY-29304), derived from Streptomyces strains AA3891 and AA6532, respectively, have been found to inhibit HIV-1 fusion and viral replication in cell c...
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The 21-amino acid peptides siamycin II (BMY-29303) and siamycin I (BMY-29304), derived from Streptomyces strains AA3891 and AA6532, respectively, have been found to inhibit HIV-1 fusion and viral replication in cell culture. The primary sequence of siamycin II is CLGIGSCNDFAGCGYAIVCFW. Siamycin I differs by only one amino acid;it has a valine residue at position 4. In both peptides, disulfide bonds link Cys(1) with Cys(13) and Cys(7) with Cys(19), and the side chain of Asp(9) forms an amide bond with the N-terminus. Siamycin II, when dissolved in a 50:50 mixture of DMSO and H2O, yields NOESY spectra with exceptional numbers of cross peaks for a peptide of this size. We have used 335 NOE distance constraints and 13 dihedral angle constraints to generate an ensemble of 30 siamycin II structures;these have average backbone atom and all heavy atom rmsd values to the mean coordinates of 0.24 and 0.52 Angstrom, respectively, The peptide displays an unusual wedge-shaped structure, with one face being predominantly hydrophobic and the other being predominantly hydrophilic. Chemical shift and NOE data show that the siamycin I structure is essentially identical to siamycin II. These peptides may act by preventing oligomerization of the HIV transmembrane glycoprotein gp41, or by interfering with interactions between gp41 and the envelope glycoprotein gp120, the cell membrane or membrane-bound proteins [Frechet, D. et al. (1994) Biochemistry, 33, 42-50]. The amphipathic nature of siamycin II and siamycin I suggests that a polar (or apolar) site on the target protein may be masked by the apolar (or polar) face of the peptide upon peptide/protein complexation.
作者：
Braun, WUniv Texas
Med Branch Sealy Ctr Struct Biol Dept Human Biol Chem & Genet Galveston TX 77555 USA
This article describes the personal memories of the author on the early developments of computational methods for protein structure determination in the laboratory of Kurt Wuthrich from 1977 to the 1990's. The com...
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This article describes the personal memories of the author on the early developments of computational methods for protein structure determination in the laboratory of Kurt Wuthrich from 1977 to the 1990's. The computational problem to solve protein structures from NMR structures needed sophisticated computational and mathematical approaches;some of the technical problems were related to the limited memory capabilities of the computer hardware at that time. Competition and collaboration between X-ray crystallographers and NMR was intensely intertwined in the early days of protein NMR, and provided the driving force to establish the NMR method as a second method for high-resolution structure determination. Kurt's vision on the power of NMR and his faith in theoreticians made his laboratory a fruitful place for co-workers with different scientific background. Copyright (C) 2003 John Wiley Sons, Ltd.
An efficient algorithm for generating DNA structures from a given set of distance constraints has been developed. The present implementation is suited for single-stranded DNA. The performance of the program has been t...
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To improve the reliability of the increasing network two disjoint paths should be found between a given source and a given destination. The problem of finding two minimum cost node-disjoint/edge -disjoint paths with d...
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ISBN:
(纸本)0819451770
To improve the reliability of the increasing network two disjoint paths should be found between a given source and a given destination. The problem of finding two minimum cost node-disjoint/edge -disjoint paths with different costs in a directed network can be formulated as a linear integer programming problem minimizing the sum of the costs on the edges in two paths, which is strongly NP-complete problem. Linear relaxation programming which relaxes the integer variables in the original programming is often applied to solve this NP problem. Comparing with linear relaxation programming, Lagrangean relaxation affords a lower bound of the objective value of original programming. Based on this a Lagrangean relaxation method for solving two disjoint paths is presented after a mathematical programming model of the problem is established. By using a modified subgradient optimization technology a new algorithm to solve the Lagrangean relaxation is put forward. The complexity of the proposed algorithm is as same as the Dijkstra's algorithm (O(n(2))). The efficiency of this algorithm is demonstrated by test examples.
作者：
Braun, WUniv Texas
Med Branch Sealy Ctr Struct Biol Dept Human Biol Chem & Genet Galveston TX 77555 USA
This article describes the personal memories of the author on the early developments of computational methods for protein structure determination in the laboratory of Kurt Wuthrich from 1977 to the 1990's. The com...
详细信息
This article describes the personal memories of the author on the early developments of computational methods for protein structure determination in the laboratory of Kurt Wuthrich from 1977 to the 1990's. The computational problem to solve protein structures from NMR structures needed sophisticated computational and mathematical approaches;some of the technical problems were related to the limited memory capabilities of the computer hardware at that time. Competition and collaboration between X-ray crystallographers and NMR was intensely intertwined in the early days of protein NMR, and provided the driving force to establish the NMR method as a second method for high-resolution structure determination. Kurt's vision on the power of NMR and his faith in theoreticians made his laboratory a fruitful place for co-workers with different scientific background. Copyright (C) 2003 John Wiley Sons, Ltd.
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