Titre :

FlexPepDock lessons from CAPRI peptide-protein rounds and suggested new criteria for assessment of model quality and utility

Auteur(s) :

Marcu, Orly [Auteur]
The Hebrew University of Jerusalem [HUJ]
Dodson, Emma-Joy [Auteur]
The Hebrew University of Jerusalem [HUJ]
Alam, Nawsad [Auteur]
The Hebrew University of Jerusalem [HUJ]
Sperber, Michal [Auteur]
The Hebrew University of Jerusalem [HUJ]
Kozakov, Dima [Auteur]
Stony Brook University [SUNY] [SBU]
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Schueler-Furman, Ora [Auteur]
The Hebrew University of Jerusalem [HUJ]

Titre de la revue :

Proteins

Nom court de la revue :

Proteins

Numéro :

85

Pagination :

445-462

Date de publication :

2017-03

ISSN :

1097-0134

Mot(s)-clé(s) en anglais :

Peptides
Peptide docking
X-ray Crystallography
Computational Biology
Benchmarking
binding hotspots
Protein Interaction Mapping
Amino Acid Motifs
Proteins
Thermodynamics
Algorithms
Capri
Hydrogen Bonding
model assessment
Protein Binding
Protein Conformation
Molecular Docking Simulation
Software
Structural Homology, Protein
Binding Sites
Research Design
FlexPepDock
impact of low-accuracy models

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie moléculaire

Résumé en anglais : [en]

CAPRI rounds 28 and 29 included, for the first time, peptide-receptor targets of three different systems, reflecting increased appreciation of the importance of peptide-protein interactions. The CAPRI rounds allowed us to ...
Lire la suite >CAPRI rounds 28 and 29 included, for the first time, peptide-receptor targets of three different systems, reflecting increased appreciation of the importance of peptide-protein interactions. The CAPRI rounds allowed us to objectively assess the performance of Rosetta FlexPepDock, one of the first protocols to explicitly include peptide flexibility in docking, accounting for peptide conformational changes upon binding. We discuss here successes and challenges in modeling these targets: we obtain top-performing, high-resolution models of the peptide motif for cases with known binding sites but there is a need for better modeling of flanking regions, as well as better selection criteria, in particular for unknown binding sites. These rounds have also provided us the opportunity to reassess the success criteria, to better reflect the quality of a peptide-protein complex model. Using all models submitted to CAPRI, we analyze the correlation between current classification criteria and the ability to retrieve critical interface features, such as hydrogen bonds and hotspots. We find that loosening the backbone (and ligand) RMSD threshold, together with a restriction on the side chain RMSD measure, allows us to improve the selection of high-accuracy models. We also suggest a new measure to assess interface hydrogen bond recovery, which is not assessed by the current CAPRI criteria. Finally, we find that surprisingly much can be learned from rather inaccurate models about binding hotspots, suggesting that the current status of peptide-protein docking methods, as reflected by the submitted CAPRI models, can already have a significant impact on our understanding of protein interactions. Proteins 2017; 85:445-462. © 2016 Wiley Periodicals, Inc.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Établissement(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Computational Molecular Systems Biology

Date de dépôt :

2020-02-12T15:11:22Z
2021-03-04T07:46:57Z