A superposition free method for protein conformational ensemble analyses and local clustering based on a differential geometry representation of backbone

Author(s)

da Silva Neto, Antonio Marinho ^{[1, 2]} ; Silva, Samuel Reghim ^[1] ; Vendruscolo, Michele ^[3] ; Camilloni, Carlo ^[4] ; Montalvao, Rinaldo Wander ^[5]

Affiliation

^[1] Univ Sao Paulo, Sao Carlos Inst Phys, Sao Carlos, SP - Brazil

^[2] Univ Warsaw, Ctr New Technol, PL-02097 Warsaw - Poland

^[3] Univ Cambridge, Dept Chem, Cambridge - England

^[4] Univ Milan, Dept Biosci, Milan - Italy

^[5] Ctr Appl Artificial Intelligence, Av Joaquim Porto Vilanova 401, BR-91410400 Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS; v. 87, n. 4, p. 302-312, APR 2019.
• Web of Science Citations: 3

Abstract

Here a differential geometry (DG) representation of protein backbone is explored on the analyses of protein conformational ensembles. The protein backbone is described by curvature, kappa, and torsion, tau, values per residue and we propose 1) a new dissimilarity and protein flexibility measurement and 2) a local conformational clustering method. The methods were applied to Ubiquitin and c-Myb-KIX protein conformational ensembles and results show that kappa\textbackslash{}tau metric space allows to properly judge protein flexibility by avoiding the superposition problem. The d(max) measurement presents equally good or superior results when compared to RMSF, especially for the intrinsically unstructured protein. The clustering method is unique as it relates protein global to local dynamics by providing a global clustering solutions per residue. The methods proposed can be especially useful to the analyses of highly flexible proteins. The software written for the analyses presented here is available at for academic usage only. (AU)

• FAPESP's process: 13/20929-4 - Determination of protein-protein complexes from sparse experimental data
• Grantee: Samuel Reghim Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/18398-0 - Determination of Protein-Protein and Protein-Ligand Complexes from Sparse Experimental Data
• Grantee: Antonio Marinho da Silva Neto
• Support Opportunities: Scholarships in Brazil - Doctorate