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Statistical Force-Field for Structural Modeling Using Chemical Cross-Linking/mass Spectrometry Distance Constraints

preprint
submitted on 26.03.2018, 19:04 and posted on 27.03.2018, 13:31 by Allan J. R. Ferrari, Fabio C. Gozzo, Leandro Martinez

Chemical cross-linking/Mass Spectrometry (XLMS) is an experimental method to obtain distance constraints between amino acid residues, which can be applied to structural modeling of tertiary and quaternary biomolecular structures. These constraints provide, in principle, only upper limits to the distance between amino acid residues along the surface of the biomolecule. In practice, attempts to use of XLMS constraints for tertiary protein structure determination have not been widely successful. This indicates the need of specifically designed strategies for the representation of these constraints within modeling algorithms. Here, a force-field designed to represent XLMS-derived constraints is proposed. The potential energy functions are obtained by computing, in the database of known protein structures, the probability of satisfaction of a topological cross-linking distance as a function of the Euclidean distance between amino acid residues. The force-field can be easily incorporated into current modeling methods and software. In this work, the force-field was implemented within the Rosetta ab initio relax protocol. We show a significant improvement in the quality of the models obtained relative to current strategies for constraint representation. This force-field contributes to the long-desired goal of obtaining the tertiary structures of proteins using XLMS data. Force-field parameters and usage instructions are freely available at http://m3g.iqm.unicamp.br/topolink/xlff

Funding

Fapesp (Grants 2010/16947-9, 2013/05475-7, 2013/08293-7, 2014/17264-3 and 2016/13195-2), and CNPq (Grant 470374/2013-6)

History

Email Address of Submitting Author

leandromartinez98@gmail.com

Email Address(es) for Other Author(s)

ajrferrari@gmail.com, fgozzo@gmail.com

Institution

Institute of Chemistry, University of Campinas

Country

Brazil

ORCID For Submitting Author

0000-0002-6857-1884

Declaration of Conflict of Interest

No conflict of interest.

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