Full Citation

Title: Summary for Policymakers

Citation Type: Book, Section

Publication Year: 2018

ISBN: 9788578110796

ISSN: 1098-6596

DOI: 10.1017/CBO9781107415324.004

NSFID:

PMCID:

PMID: 25246403

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.

Url: https://paa.confex.com/paa/2018/mediafile/ExtendedAbstract/Paper23281/Roehrkasse_MWPA.pdf

Url: https://www.cambridge.org/core/product/identifier/CBO9781107415324A009/type/book_part

User Submitted?: No

Authors: Roehrkasse, Alezander F.

Editors: Intergovernmental Panel on Climate Change,

Pages: 1-30

Volume Title: Climate Change 2013 - The Physical Science Basis

Publisher: Cambridge University Press

Publisher Location: Cambridge

Volume:

Edition:

Data Collections: IPUMS USA

Topics: Family and Marriage, Gender

Countries: United States