Improved docking of polypeptides with Glide.
J Chem Inf Model
; 53(7): 1689-99, 2013 Jul 22.
Article
em En
| MEDLINE
| ID: mdl-23800267
ABSTRACT
Predicting the binding mode of flexible polypeptides to proteins is an important task that falls outside the domain of applicability of most small molecule and protein-protein docking tools. Here, we test the small molecule flexible ligand docking program Glide on a set of 19 non-α-helical peptides and systematically improve pose prediction accuracy by enhancing Glide sampling for flexible polypeptides. In addition, scoring of the poses was improved by post-processing with physics-based implicit solvent MM-GBSA calculations. Using the best RMSD among the top 10 scoring poses as a metric, the success rate (RMSD ≤ 2.0 Å for the interface backbone atoms) increased from 21% with default Glide SP settings to 58% with the enhanced peptide sampling and scoring protocol in the case of redocking to the native protein structure. This approaches the accuracy of the recently developed Rosetta FlexPepDock method (63% success for these 19 peptides) while being over 100 times faster. Cross-docking was performed for a subset of cases where an unbound receptor structure was available, and in that case, 40% of peptides were docked successfully. We analyze the results and find that the optimized polypeptide protocol is most accurate for extended peptides of limited size and number of formal charges, defining a domain of applicability for this approach.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Software
/
Simulação de Acoplamento Molecular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article