EXTENSIVE DISTANCE GEOMETRY CALCULATIONS WITH DIFFERENT NOE CALIBRATIONS - NEW CRITERIA FOR STRUCTURE SELECTION APPLIED TO SANDOSTATIN AND BPTI

被引:46
作者
WIDMER, H [1 ]
WIDMER, A [1 ]
BRAUN, W [1 ]
机构
[1] SWISS FED INST TECHNOL,INST GEOL,CH-8093 ZURICH,SWITZERLAND
关键词
NMR STRUCTURE DETERMINATION; STRUCTURE SELECTION; DISTANCE GEOMETRY; NOE CALIBRATION; SANDOSTATIN;
D O I
10.1007/BF00212517
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To generate structures efficiently, a version of the distance geometry program DIANA for a parallel computer was developed, new objective criteria for the selection of NMR solution structures are presented, and the influence of using different calibrations of NOE intensities on the final structures are described. The methods are applied to the structure determination of Sandostatin, a disulfide-bridged octapeptide, and to model calculations of BPTI. On an Alliant FX2800 computer using 10 processors in parallel, the calculations were done 9.2 times faster than with a single processor. Up to 7000 Sandostatin structures were calculated with distance and angular constraints. The procedure for selecting acceptable structures is based on the maximum values of pairwise RMSDs between structures. Suitable target function cut-offs are defined independent of the number of starting structures. The method allowed for an objective comparison of three groups of Sandostatin structures that were calculated from different sets of upper distance constraints which were derived from the same NOE intensity data using three empirical calibration curves. The number of converged structures and the target function values differed significantly among the three groups, but the structures were qualitatively and quantitatively very similar. The conformation is well deter-mined in the cyclic region Cys2-Cys7 and adopts a beta-turn centered at D-Trp4-Lys5. The criteria for structure selection were further tested with BPTI. Results obtained from sets of structures calculated with and without using the REDAC strategy are consistent and suggest that the structure selection method is objective and generally applicable.
引用
收藏
页码:307 / 324
页数:18
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