However, for many of the known structures, functions are not yet determined, and in many modelling tasks, an accurate structural model does not necessarily tell us about function. Thus, there see more is a pressing need for high-throughput methods for determining function from structure. The spatial arrangement of key amino acids in a folded protein, on the surface or buried in clefts, is often the
determinants of its biological function. A central aim of molecular biology is to understand the relationship between such substructures or surfaces and biological function, leading both to function prediction and to function design. We present a new general method for discovering the features of binding pockets that confer specificity for particular ligands. Using a recently developed machine-learning technique which couples the rule-discovery approach of inductive logic programming with the statistical learning power of support vector machines, we are A-1210477 able to discriminate, with high precision (90%) and recall (86%) between pockets that bind FAD and those that bind NAD on a large benchmark set given only the geometry and composition of the backbone of the binding pocket without the use of docking. In addition, we learn rules governing this specificity which can feed into protein functional design protocols. An analysis of the rules found suggests that key features of the binding
pocket may be tied to conformational freedom in the ligand. The representation is sufficiently general to be applicable to any discriminatory binding problem. All programs and data sets are freely available to non-commercial ASK1 users at http://www.sbg.bio.ic.ac.uk/svilp_ligand.”
“Purpose: We characterized continence, satisfaction and adverse events in women at least 5 years after Burch urethropexy or fascial sling with longitudinal followup of randomized clinical trial participants.
Materials and Methods: Of 655 women who participated in a randomized surgical trial comparing the efficacy of the Burch and sling treatments 482 (73.6%) enrolled in this long-term observational study. Urinary
continence status was assessed yearly for a minimum of 5 years postoperatively. Continence was defined as no urinary leakage on a 3-day voiding diary, and no self-reported stress incontinence symptoms and no stress incontinence surgical re-treatment.
Results: Incontinent participants were more likely to enroll in the followup study than continent patients (85.5% vs 52.2%) regardless of surgical group (p <0.0001). Overall the continence rates were lower in the Burch urethropexy group than in the fascial sling group (p = 0.002). The continence rates at 5 years were 24.1% (95% CI 18.5 to 29.7) vs 30.8% (95% CI 24.7 to 36.9), respectively. Satisfaction at 5 years was related to continence status and was higher in women undergoing sling surgery (83% vs 73%, p = 0.04). Satisfaction decreased with time (p = 0.001) and remained higher in the sling group (p = 0.03).