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

submitted on 26.03.2018 and posted on 27.03.2018 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


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


Email Address of Submitting Author

Email Address(es) for Other Author(s),


Institute of Chemistry, University of Campinas



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest.