Enhancing protein fold determination by exploring the complementary information of chemical cross-linking and coevolutionary signals

Author(s)

dos Santos, Ricardo N. ^{[1, 2]} ; Ferrari, Allan J. R. ^[1] ; de Jesus, Hugo C. R. ^[1] ; Gozzo, Fabio C. ^[1] ; Morcos, Faruck ^[3] ; Martinez, Leandro ^{[1, 2]}

Affiliation

^[1] Univ Estadual Campinas, Inst Chem, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Ctr Computat Engn & Sci, BR-13083970 Campinas, SP - Brazil

^[3] Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75080 - USA

• Document type: Journal article
• Source: Bioinformatics; v. 34, n. 13, p. 2201-2208, JUL 1 2018.
• Web of Science Citations: 6

Abstract

Motivation: Elucidation of protein native states from amino acid sequences is a primary computational challenge. Modern computational and experimental methodologies, such as molecular coevolution and chemical cross-linking mass-spectrometry allowed protein structural characterization to previously intangible systems. Despite several independent successful examples, data from these distinct methodologies have not been systematically studied in conjunction. One challenge of structural inference using coevolution is that it is limited to sequence fragments within a conserved and unique domain for which sufficient sequence datasets are available. Therefore, coupling coevolutionary data with complimentary distance constraints from orthogonal sources can provide additional precision to structure prediction methodologies. Results: In this work, we present a methodology to combine residue interaction data obtained from coevolutionary information and cross-linking/mass spectrometry distance constraints in order to identify functional states of proteins. Using a combination of structure-based models (SBMs) with optimized Gaussian-like potentials, secondary structure estimation and simulated annealing molecular dynamics, we provide an automated methodology to integrate constraint data from diverse sources in order to elucidate the native conformation of full protein systems with distinct complexity and structural topologies. We show that cross-linking mass spectrometry constraints improve the structure predictions obtained from SBMs and coevolution signals, and that the constraints obtained by each method have a useful degree of complementarity that promotes enhanced fold estimates. (AU)

• FAPESP's process: 13/08293-7 - CCES - Center for Computational Engineering and Sciences
• Grantee: Munir Salomao Skaf
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 13/05475-7 - Computational methods in optimization
• Grantee: Sandra Augusta Santos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/13195-2 - Modeling of protein structure and protein complexes using mass spectrometry data
• Grantee: Allan Jhonathan Ramos Ferrari
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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 Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/13667-9 - Studies of multimeric protein systems through cross-linking, mass spectrometry and molecular modeling
• Grantee: Ricardo Nascimento dos Santos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 10/16947-9 - Correlations between dynamics, structure and function in protein: computer simulations and algorithms
• Grantee: Leandro Martinez
• Support Opportunities: Regular Research Grants