Protein structure elucidation from NMR proton densities
| Autor: | Miguel Llinás, Alexander Grishaev |
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| Rok vydání: | 2002 |
| Předmět: |
Models
Molecular Multidisciplinary Proton Chemistry Chemical shift Proteins Biological Sciences Protein Structure Tertiary Molecular dynamics Crystallography Protein structure Kringles Proton NMR Side chain Molecule Computer Simulation Protons Nuclear Magnetic Resonance Biomolecular Heteronuclear single quantum coherence spectroscopy |
| Zdroj: | Proceedings of the National Academy of Sciences. 99:6713-6718 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. H N atoms are readily recognizable from 1 H/ 2 H exchange or 1 H/ 15 N heteronuclear single quantum correlation (HSQC) experiments. The primary structure is threaded through the unassigned foc by leapfrogging along peptidyl amide H N s and the connected H α s. Via a Bayesian approach, the probabilities of the sequential connectivity hypotheses are inferred from likelihoods of H N /H N , H N /H α , and H α /H α interatomic distances as well as 1 H 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 Å (backbone heavy atoms) and 1.5–2.0 Å (all heavy atoms) rms deviations from reported x-ray and/or NMR structures. |
| Databáze: | OpenAIRE |
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