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.
CITATION STYLE
Belgrano, A., Clausen, P., Ejdung, G., Gamfeldt, L., Gundersen, H., Hammer, M., … Vävare, S. (2018). Biodiversity and ecosystem services in Nordic coastal ecosystems: an IPBES-like assessment. Volume 1. The general overview. (A. Belgrano, Ed.), BMC Public Health (Vol. 5, pp. 1–8). Nordic Council of Ministers. Retrieved from https://ejournal.poltektegal.ac.id/index.php/siklus/article/view/298%0Ahttp://repositorio.unan.edu.ni/2986/1/5624.pdf%0Ahttp://dx.doi.org/10.1016/j.jana.2015.10.005%0Ahttp://www.biomedcentral.com/1471-2458/12/58%0Ahttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&P
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