The history of life: A very short Introduction
Oxford, 2008
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.
Quotes from this work
[A]ll living things fall into […] three great domains. The Domain Bacteria includes Cyanobacteria and most groups commonly called bacteria. The Domain Archaea (‘ancient ones’) comprises the Halobacteria (salt-digesters), Methanobacteria (methane-producers), Eocytes (heat-loving sulphur-metabolizing bacteria), and others. The Domain Eucarya includes an array of single-celled forms that are often lumped together as ‘algae’, as well as multicellular organisms. Perhaps the most startling observation is that, within Eucarya, the fungi are more closely related to the animals than to the plants, and this has been confirmed in several analyses. This poses a moral dilemma for vegetarians: should they eat mushrooms or not.