Statistical force-field for structural modeling using chemical cross-linking/mass spectrometry distance constraints

Author(s)

Ferrari, Allan J. R. ^[1] ; Gozzo, Fabio C. ^[1] ; Martinez, Leandro ^{[1, 2]}

Affiliation

^[1] Univ Estadual Campinas, Inst Chem, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Ctr Comp Engn & Sci, Campinas, SP - Brazil

• Document type: Journal article
• Source: Bioinformatics; v. 35, n. 17, p. 3005-3012, SEP 1 2019.
• Web of Science Citations: 3

Abstract

Motivation: 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. Results: 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. First, the strategy suggests that XL constraints should be set to shorter distances than usually assumed. Second, the complete statistical force-field improves the models obtained and can be easily incorporated into current modeling methods and software. The force-field was implemented and is distributed to be used within the Rosetta ab initio relax protocol. (AU)

• FAPESP's process: 13/05475-7 - Computational methods in optimization
• Grantee: Sandra Augusta Santos
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 18/14274-9 - Protein Structure Determination from Distance Constraints Derived from Chemical Cross-linking: Computational Methods and Applications
• Grantee: Leandro Martinez
• Support type: Regular Research Grants
• FAPESP's process: 14/17264-3 - New frontiers in structural proteomics: characterizing protein and protein complex structures by mass spectrometry
• Grantee: Fabio Cesar Gozzo
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 13/08293-7 - CCES - Center for Computational Engineering and Sciences
• Grantee: Munir Salomao Skaf
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/13195-2 - Modeling of protein structure and protein complexes using mass spectrometry data
• Grantee: Allan Jhonathan Ramos Ferrari
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/23814-3 - Structural caracterization of Stanniocalcin-1 by advanced structural proteomics
• Grantee: Allan Jhonathan Ramos Ferrari
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 10/16947-9 - Correlations between dynamics, structure and function in protein: computer simulations and algorithms
• Grantee: Leandro Martinez
• Support type: Regular Research Grants