Protein Docking by the Underestimation of Free Energy Funnels in the Space of Encounter Complexes

Similarly to protein folding, the association of two proteins is driven by a free energy funnel, determined by favorable interactions in some neighborhood of the native state. We describe a docking method based on stochastic global minimization of funnel-shaped energy functions in the space of rigid body motions (SE(3)) while accounting for flexibility of the interface side chains. The method, called semi-definite programming-based underestimation (SDU), employs a general quadratic function to underestimate a set of local energy minima and uses the resulting underestimator to bias further sampling. While SDU effectively minimizes functions with funnel-shaped basins, its application to docking in the rotational and translational space SE(3) is not straightforward due to the geometry of that space. We introduce a strategy that uses separate independent variables for side-chain optimization, center-to-center distance of the two proteins, and five angular descriptors of the relative orientations of the molecules. The removal of the center-to-center distance turns out to vastly improve the efficiency of the search, because the five-dimensional space now exhibits a well-behaved energy surface suitable for underestimation. This algorithm explores the free energy surface spanned by encounter complexes that correspond to local free energy minima and shows similarity to the model of macromolecular association that proceeds through a series of collisions. Results for standard protein docking benchmarks establish that in this space the free energy landscape is a funnel in a reasonably broad neighborhood of the native state and that the SDU strategy can generate docking predictions with less than 5 � ligand interface Ca root-mean-square deviation while achieving an approximately 20-fold efficiency gain compared to Monte Carlo methods.

Accurate and Efficient Gesture Spotting via Pruning and Subgesture Reasoning

Gesture spotting is the challenging task of locating the start and end frames of the video stream that correspond to a gesture of interest, while at the same time rejecting non-gesture motion patterns. This paper proposes a new gesture spotting and recognition algorithm that is based on the continuous dynamic programming (CDP) algorithm, and runs in real-time. To make gesture spotting efficient a pruning method is proposed that allows the system to evaluate a relatively small number of hypotheses compared to CDP. Pruning is implemented by a set of model-dependent classifiers, that are learned from training examples. To make gesture spotting more accurate a subgesture reasoning process is proposed that models the fact that some gesture models can falsely match parts of other longer gestures. In our experiments, the proposed method with pruning and subgesture modeling is an order of magnitude faster and 18% more accurate compared to the original CDP algorithm.