Details zur Publikation |
| Kategorie | Textpublikation |
| Referenztyp | Zeitschriften |
| DOI | 10.1016/j.ymeth.2015.05.014 |
| Volltext | Autorenversion |
| Titel (primär) | Protein structure prediction guided by crosslinking restraints – A systematic evaluation of the impact of the crosslinking spacer length |
| Autor | Hofmann, T.; Fischer, A.W.; Meiler, J.; Kalkhof, S. |
| Quelle | Methods |
| Erscheinungsjahr | 2015 |
| Department | PROTEOM |
| Band/Volume | 89 |
| Seite von | 79 |
| Seite bis | 90 |
| Sprache | englisch |
| Keywords | Crosslinking; Protein structure prediction; De novo folding; Mass spectrometry; Protein modeling |
| UFZ Querschnittsthemen | RU3; |
| Abstract | Recent development of high-resolution mass spectrometry
(MS) instruments enables chemical crosslinking (XL) to become a
high-throughput method for obtaining structural information about
proteins. Restraints derived from XL-MS experiments have been used
successfully for structure refinement and protein–protein docking.
However, one formidable question is under which circumstances XL-MS data
might be sufficient to determine a protein’s tertiary structure de novo? Answering this question will not only include understanding the impact of XL-MS data on sampling and scoring within a de novo
protein structure prediction algorithm, it must also determine an
optimal crosslinker type and length for protein structure determination.
While a longer crosslinker will yield more restraints, the value of
each restraint for protein structure prediction decreases as the
restraint is consistent with a larger conformational space. In this study, the number of crosslinks and their discriminative power was systematically analyzed in silico on a set of 2055 non-redundant protein folds considering Lys–Lys, Lys–Asp, Lys–Glu, Cys–Cys, and Arg–Arg reactive crosslinkers between 1 and 60 Å. Depending on the protein size a heuristic was developed that determines the optimal crosslinker length. Next, simulated restraints of variable length were used to de novo predict the tertiary structure of fifteen proteins using the BCL::Fold algorithm. The results demonstrate that a distinct crosslinker length exists for which information content for de novo protein structure prediction is maximized. The sampling accuracy improves on average by 1.0 Å and up to 2.2 Å in the most prominent example. XL-MS restraints enable consistently an improved selection of native-like models with an average enrichment of 2.1. |
| dauerhafte UFZ-Verlinkung | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=16181 |
| Hofmann, T., Fischer, A.W., Meiler, J., Kalkhof, S. (2015): Protein structure prediction guided by crosslinking restraints – A systematic evaluation of the impact of the crosslinking spacer length Methods 89 , 79 - 90 10.1016/j.ymeth.2015.05.014 |
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