Protein Structure Determination from Distance Constraints Derived from Chemical Cross-linking: Computational Methods and Applications

• Grant number: 18/14274-9
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2018
• End date: October 31, 2020
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Leandro Martinez
• Grantee: Leandro Martinez
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• City of the host institution: Campinas

Abstract

Molecular modeling methods are an integral part of strategies for the determination of protein structures, with or without the use of experimental data. The extent of the role of modeling methods depends on the structural resolution of the experimental data. If the experimental data provides very precise information on the structure, the modeling strategies are used only to finely adjust the structure or model minor fragments. This is common, for example, in protein structure determination by protein X-ray crystallography. On the other side, when the structural information is of lower resolution, the modeling strategies assume a central role. For example, they are intrinsic parts of the process of determining protein structures from NMR, cryoelectron microscopy or low resolution data as small angle X-ray scattering or circular dichroism. More recently, chemical crosslinking experiments, analyzed by mass spectrometry, have been developed to obtain distance restraints that can be, in principle, used to to aid the determination of protein tridimensional structures. These data has been shown to be useful for the determination of the relative orientation of structures in protein complexes, but their use for tertiary structure resolution is not yet successful. In this project, we propose the development of a series of computational strategies to address the limitations of the information provided by chemical crosslinking/mass spectrometry for the determination of protein tertiary structures. Protocols for modeling, force-fields, and statistical methods for the classification and analysis of experimental data are proposed, which take into consideration the structural nature and the resolution of these experimental restraints. (AU)

Scientific publications

(12)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

MARTINEZ, LEANDRO. omplexMixtures.jl: Investigating the structure of solutions of complex-shaped molecules from a solvent-shell perspectiv. JOURNAL OF MOLECULAR LIQUIDS, v. 347, FEB 1 2022. (10/16947-9, 18/14274-9, 18/24293-0, 13/08293-7)

DOS SANTOS, RICARDO N.; BOTTINO, GUILHERME F.; GOZZO, FABIO C.; MORCOS, FARUCK; MARTINEZ, LEANDRO. Structural complementarity of distance constraints obtained from chemical cross-linking and amino acid coevolution. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, v. 88, n. 4, NOV 2019. (18/14274-9, 10/16947-9, 15/13667-9, 18/24293-0, 13/08293-7, 14/17264-3)

PEREIRA, ANDER F.; PICCOLI, VINICIUS; MARTINEZ, LEANDRO. Trifluoroethanol direct interactions with protein backbones destabilize a-helices. JOURNAL OF MOLECULAR LIQUIDS, v. 365, p. 11-pg., 2022-09-01. (20/04549-0, 20/04916-3, 18/14274-9, 18/24293-0, 13/08293-7, 10/16947-9)

BOTTINO, GUILHERME F.; FERRARI, ALLAN J. R.; GOZZO, FABIO C.; MARTINEZ, LEANDRO. Structural discrimination analysis for constraint selection in protein modeling. Bioinformatics, v. 37, n. 21, p. 3766-3773, NOV 1 2021. (13/08293-7, 16/13195-2, 19/17007-4, 10/16947-9, 18/14274-9)

FERRARI, ALLAN J. R.; GOZZO, FABIO C.; MARTINEZ, LEANDRO. Statistical force-field for structural modeling using chemical cross-linking/mass spectrometry distance constraints. Bioinformatics, v. 35, n. 17, p. 3005-3012, SEP 1 2019. (13/08293-7, 13/05475-7, 18/14274-9, 16/13195-2, 14/17264-3, 13/23814-3, 10/16947-9)

FERRARI, ALLAN J. R.; CLASEN, MILAN A.; KURT, LOUISE; CARVALHO, PAULO C.; GOZZO, FABIO C.; MARTINEZ, LEANDRO. TopoLink: evaluation of structural models using chemical crosslinking distance constraints. Bioinformatics, v. 35, n. 17, p. 3169-3170, SEP 1 2019. (13/08293-7, 13/05475-7, 18/14274-9, 16/13195-2, 10/16947-9)

PICCOLI, VINICIUS; MARTINEZ, LEANDRO. Ionic liquid solvation of proteins in native and denatured states. JOURNAL OF MOLECULAR LIQUIDS, v. 363, p. 15-pg., 2022-07-30. (20/04916-3, 13/08293-7, 18/24293-0, 18/14274-9, 10/16947-9)

PEREIRA, ANDER FRANCISCO; MARTINEZ, LEANDRO. Helical Content Correlations and Hydration Structures of the Folding Ensemble of the B Domain of Protein A. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 64, n. 8, p. 10-pg., 2024-04-03. (10/16947-9, 20/04549-0, 18/14274-9, 18/24293-0, 13/08293-7)

SONORA, MARTIN; MARTINEZ, LEANDRO; PANTANO, SERGIO; MACHADO, MATIAS R.. Wrapping Up Viruses at Multiscale Resolution: Optimizing PACKMOL and SIRAH Execution for Simulating the Zika Virus. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 61, n. 1, p. 408-422, JAN 25 2021. (10/16947-9, 13/08293-7, 18/14274-9, 18/24293-0)

MARTINEZ, LEANDRO. CellListMap.jl: Efficient and customizable cell list implementation for calculation of pairwise particle properties within a cutoff. COMPUTER PHYSICS COMMUNICATIONS, v. 279, p. 12-pg., 2022-10-01. (10/16947-9, 13/08293-7, 18/14274-9, 18/24293-0)

PEREIRA, ANDER FRANCISCO; MARTINEZ, LEANDRO. Osmolyte Structural and Thermodynamic Effects Across the Protein Folding Landscape. JACS AU, v. N/A, p. 17-pg., 2025-10-13. (18/14274-9, 19/17874-0, 13/08293-7, 18/24293-0, 20/04549-0)

PICCOLI, VINICIUS; MARTINEZ, LEANDRO. Cation Hydrophobicity Effects on Protein Solvation in Aqueous Ionic Liquids. Journal of Physical Chemistry B, v. 129, n. 27, p. 12-pg., 2025-05-29. (13/08293-7, 18/24293-0, 20/04916-3, 19/17874-0, 18/14274-9)