Format

Send to

Choose Destination
Sci Rep. 2017 Aug 18;7(1):8826. doi: 10.1038/s41598-017-08366-3.

Exploring the Sequence-based Prediction of Folding Initiation Sites in Proteins.

Raimondi D1,2,3,4, Orlando G1,2,3,4, Pancsa R5, Khan T1,3,4, Vranken WF6,7,8.

Author information

1
Interuniversity Institute of Bioinformatics in Brussels, ULB/VUB, Triomflaan, BC building, 6th floor, CP 263, 1050, Brussels, Belgium.
2
Machine Learning Group, Université Libre de Bruxelles, Boulevard du Triomphe, CP 212, 1050, Brussels, Belgium.
3
Centre for Structural Biology, VIB, Pleinlaan 2, 1050, Brussels, Belgium.
4
Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium.
5
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0QH, United Kingdom.
6
Interuniversity Institute of Bioinformatics in Brussels, ULB/VUB, Triomflaan, BC building, 6th floor, CP 263, 1050, Brussels, Belgium. wvranken@vub.ac.be.
7
Centre for Structural Biology, VIB, Pleinlaan 2, 1050, Brussels, Belgium. wvranken@vub.ac.be.
8
Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium. wvranken@vub.ac.be.

Abstract

Protein folding is a complex process that can lead to disease when it fails. Especially poorly understood are the very early stages of protein folding, which are likely defined by intrinsic local interactions between amino acids close to each other in the protein sequence. We here present EFoldMine, a method that predicts, from the primary amino acid sequence of a protein, which amino acids are likely involved in early folding events. The method is based on early folding data from hydrogen deuterium exchange (HDX) data from NMR pulsed labelling experiments, and uses backbone and sidechain dynamics as well as secondary structure propensities as features. The EFoldMine predictions give insights into the folding process, as illustrated by a qualitative comparison with independent experimental observations. Furthermore, on a quantitative proteome scale, the predicted early folding residues tend to become the residues that interact the most in the folded structure, and they are often residues that display evolutionary covariation. The connection of the EFoldMine predictions with both folding pathway data and the folded protein structure suggests that the initial statistical behavior of the protein chain with respect to local structure formation has a lasting effect on its subsequent states.

PMID:
28821744
PMCID:
PMC5562875
DOI:
10.1038/s41598-017-08366-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center