130 research outputs found
Fast and accurate prediction of protein side-chain conformations
No full textAbstract
Summary: We developed a fast and accurate side-chain modeling program [Optimized Side Chain Atomic eneRgy (OSCAR)-star] based on orientation-dependent energy functions and a rigid rotamer model. The average computing time was 18 s per protein for 218 test proteins with higher prediction accuracy (1.1% increase for χ1 and 0.8% increase for χ1+2) than the best performing program developed by other groups. We show that the energy functions, which were calibrated to tolerate the discrete errors of rigid rotamers, are appropriate for protein loop selection, especially for decoys without extensive structural refinement.
Availability: OSCAR-star and the 218 test proteins are available for download at http://sysimm.ifrec.osaka-u.ac.jp/OSCAR
Contact: [email protected]
Supplementary information: Supplementary data are available at Bioinformatics online.</jats:p
2SCP-07 Intrinsic disorder mediates cooperative signal transduction in STIM1(Prediction and analysis of protein functions from structural bioinformatics,Symposium,The 52th Annual Meeting of the Biophysical Society of Japan(BSJ2014))
No full textLonidamine, a Novel Modulator for the BvgAS System of Bordetella Species
No full textThe Gram-negative bacteria Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory diseases in various mammals. They share the BvgAS two-component system, which regulates the phenotypic conversion between the virulent Bvg+ and avirulent Bvg– phases. In the BvgAS system, the sensor kinase BvgS senses environmental cues and transduces a phosphorelay signal to the response regulator BvgA, which leads to the expression of Bvg+ phase-specific genes, including virulence factor genes. Bacteria grown at 37°C exhibit the Bvg+ phenotype. In contrast, at lower than 26°C or in the presence of modulators, such as MgSO4 and nicotinic acid, the BvgAS system is inactivated, leading bacteria to the avirulent Bvg– phase. Therefore, effective modulators are expected to provide a therapeutic measure for Bordetella infection; however, no such modulators are currently available, and the mechanism by which modulators inactivate the BvgAS system is poorly understood. In the present study, we identified lonidamine as a novel modulator after screening an FDA-approved drug library using bacterial reporter systems with the Bvg+-specific and Bvg–-specific promoters. Lonidamine directly bound to the VFT2 domain of BvgS and inactivated the BvgAS system at concentrations as low as 50 nM, which was at least 2000- to 20,000-fold lower than the effective concentrations of known modulators. Lonidamine significantly reduced the adherence of B. pertussis to cultured cells but unexpectedly exacerbated bacterial colonization of the mouse nasal septum. These results provide insights into the structural requirements for BvgAS modulators and the role of Bvg phenotypes in the establishment of infection.Citation: Natsuko Ota, Takashi Nishida, Daron M. Standley, Aalaa Alrahman Sherif, Satoshi Iwano, Dendi Krisna Nugraha, Toshiya Ueno, Yasuhiko Horiguchi, Lonidamine, a Novel Modulator for the BvgAS System of Bordetella Species, Microbiology and Immunology, 69(3), 133-147, 2024-12-15, https://doi.org/10.1111/1348-0421.1319
Protein Side Chain Modeling with Orientation-Dependent Atomic Force Fields Derived by Series Expansions
No full textWe describe the development of new force fields for protein side chain modeling called optimized side chain atomic energy (OSCAR). The distance-dependent energy functions (OSCAR-d) and side-chain dihedral angle potential energy functions were represented as power and Fourier series, respectively. The resulting 802 adjustable parameters were optimized by discriminating the native side chain conformations from non-native conformations, using a training set of 12,000 side chains for each residue type. In the course of optimization, for every residue, its side chain was replaced by varying rotamers, whereas conformations for all other residues were kept as they appeared in the crystal structure. Then, the OSCAR-d were multiplied by an orientation-dependent function to yield OSCAR-o. A total of 1087 parameters of the orientation-dependent energy functions (OSCAR-o) were optimized by maximizing the energy gap between the native conformation and subrotamers calculated as low energy by OSCARd. When OSCAR-o with optimized parameters were used to model side chain conformations simultaneously for 218 recently released protein structures, the prediction accuracies were 88.8% for v1, 79.7% for v1 1 2, 1.24 A verall root mean square deviation (RMSD), and 0.62 A ࠒMSD for core residues, respectively, compared with the next-best performing side-chain modeling program which achieved 86.6% for v1, 75.7% for v1 1 2, 1.40 A verall RMSD, and 0.86 A ࠒMSD for core residues, respectively. The continuous energy functions obtained in this study are suitable for gradient-based optimization techniques for protein structure refinement.Full Tex
GASH: An improved algorithm for maximizing the number of equivalent residues between two protein structures
No full textAbstract Background We introduce GASH, a new, publicly accessible program for structural alignment and superposition. Alignments are scored by the Number of Equivalent Residues (NER), a quantitative measure of structural similarity that can be applied to any structural alignment method. Multiple alignments are optimized by conjugate gradient maximization of the NER score within the genetic algorithm framework. Initial alignments are generated by the program Local ASH, and can be supplemented by alignments from any other program. Results We compare GASH to DaliLite, CE, and to our earlier program Global ASH on a difficult test set consisting of 3,102 structure pairs, as well as a smaller set derived from the Fischer-Eisenberg set. The extent of alignment crossover, as well as the completeness of the initial set of alignments are examined. The quality of the superpositions is evaluated both by NER and by the number of aligned residues under three different RMSD cutoffs (2,4, and 6Å). In addition to the numerical assessment, the alignments for several biologically related structural pairs are discussed in detail. Conclusion Regardless of which criteria is used to judge the superposition accuracy, GASH achieves the best overall performance, followed by DaliLite, Global ASH, and CE. In terms of CPU usage, DaliLite CE and GASH perform similarly for query proteins under 500 residues, but for larger proteins DaliLite is faster than GASH or CE. Both an http interface and a simple object application protocol (SOAP) interface to the GASH program are available at http://www.pdbj.org/GASH/.</p
1P481 Real-time Structure Based Queries at the Protein Data Bank japan(23. Bioinformatics, genomics and proteomics (I),Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)
No full textDegree of pyramidality governs the height and peak position of the free-energy-barrier for the cis–trans isomerization of N-Methylacetamide
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