Personality: What makes you the way you are
Oxford, 2007
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
Why would the amount you worry about disease be a significant predictor of the a mount you worry about social relationships? After all, you might have had a history of dependable and reliable relationships, but some unsettling brushes with disease. The answer must be that the menta mechanisms that underlie worrying about disease share brain circuitry with the mental mechanisms that underlie worrying about other things. Any variation in the responsiveness of those shared circuits will show up in all kinds of worrying, not just one kind. It’s a bit like a car. The handbrake and the footbrake do different jobs and have some separate components, but they also rely on the same hydraulic system. As a consequence, a loss of brake-fluid pressure will show up in reduced effectiveness in both brakes. The more two components draw on shared machinery, the greater the extent to which the performance of one will be a predictor of the performance of the other.
One of the key goals of feminism has been equity. That is, a man or a woman with the same set of aptitudes and motivations should have an equal chance of succeeding. We can endorse this without reservation. However, this does not mean that men and women on average actually have the same motivations, so we should not necessarily expect equal sex representation across all sectors of society. A second goal of feminism has been to celebrate and validate women’s values, which are often different from those of men. It is surely more important to value the pro-social orientation many women […] possess, than it is to lament that they are not more like men.