期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：10
页码：6713-6718
DOI：10.1073/pnas.042114399
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The NMR-generated foc proton density affords a template to which the molecule has to be fitted to derive the structure. Here we present a computational protocol that achieves this goal. HN atoms are readily recognizable from 1H/2H exchange or 1H/15N heteronuclear single quantum correlation (HSQC) experiments. The primary structure is threaded through the unassigned foc by leapfrogging along peptidyl amide HNs and the connected Hs. Via a Bayesian approach, the probabilities of the sequential connectivity hypotheses are inferred from likelihoods of HN/HN, HN/H, and H/H interatomic distances as well as 1H NMR chemical shifts, both derived from public databases. Once the polypeptide sequence is identified, directionality becomes established, and the foc N and C termini are recognized. After a similar procedure, side chain H atoms are found, including discriminated cis/trans proline loci. The folded structure then is derived via a direct molecular dynamics embedding into mirror image-related representations of the foc and selected according to a lowest energy criterion. The method was applied to foc densities calculated for two protein domains, col 2 and kringle 2. The obtained structures are within 1.0-1.5 A (backbone heavy atoms) and 1.5-2.0 A (all heavy atoms) rms deviations from reported x-ray and/or NMR structures.
关键词：NMR direct method|NMR Bayesian analysis|NOE-only molecular structure|proteomics|structural genomics
