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.

Specialized Mappings Architecture with Applications to Vision-based Estimation of Articulated Body Pose

A fundamental task of vision systems is to infer the state of the world given some form of visual observations. From a computational perspective, this often involves facing an ill-posed problem; e.g., information is lost via projection of the 3D world into a 2D image. Solution of an ill-posed problem requires additional information, usually provided as a model of the underlying process. It is important that the model be both computationally feasible as well as theoretically well-founded. In this thesis, a probabilistic, nonlinear supervised computational learning model is proposed: the Specialized Mappings Architecture (SMA). The SMA framework is demonstrated in a computer vision system that can estimate the articulated pose parameters of a human body or human hands, given images obtained via one or more uncalibrated cameras. The SMA consists of several specialized forward mapping functions that are estimated automatically from training data, and a possibly known feedback function. Each specialized function maps certain domains of the input space (e.g., image features) onto the output space (e.g., articulated body parameters). A probabilistic model for the architecture is first formalized. Solutions to key algorithmic problems are then derived: simultaneous learning of the specialized domains along with the mapping functions, as well as performing inference given inputs and a feedback function. The SMA employs a variant of the Expectation-Maximization algorithm and approximate inference. The approach allows the use of alternative conditional independence assumptions for learning and inference, which are derived from a forward model and a feedback model. Experimental validation of the proposed approach is conducted in the task of estimating articulated body pose from image silhouettes. Accuracy and stability of the SMA framework is tested using artificial data sets, as well as synthetic and real video sequences of human bodies and hands.

Computing a Uniform Scaling Parameter for 3D Registration of Lung Surfaces

A difficulty in lung image registration is accounting for changes in the size of the lungs due to inspiration. We propose two methods for computing a uniform scale parameter for use in lung image registration that account for size change. A scaled rigid-body transformation allows analysis of corresponding lung CT scans taken at different times and can serve as a good low-order transformation to initialize non-rigid registration approaches. Two different features are used to compute the scale parameter. The first method uses lung surfaces. The second uses lung volumes. Both approaches are computationally inexpensive and improve the alignment of lung images over rigid registration. The two methods produce different scale parameters and may highlight different functional information about the lungs.

Quantum Monte Carlo in the Interaction Representation --- Application to a Spin-Peierls Model

A quantum Monte Carlo algorithm is constructed starting from the standard perturbation expansion in the interaction representation. The resulting configuration space is strongly related to that of the Stochastic Series Expansion (SSE) method, which is based on a direct power series expansion of exp(-beta*H). Sampling procedures previously developed for the SSE method can therefore be used also in the interaction representation formulation. The new method is first tested on the S=1/2 Heisenberg chain. Then, as an application to a model of great current interest, a Heisenberg chain including phonon degrees of freedom is studied. Einstein phonons are coupled to the spins via a linear modulation of the nearest-neighbor exchange. The simulation algorithm is implemented in the phonon occupation number basis, without Hilbert space truncations, and is exact. Results are presented for the magnetic properties of the system in a wide temperature regime, including the T-->0 limit where the chain undergoes a spin-Peierls transition. Some aspects of the phonon dynamics are also discussed. The results suggest that the effects of dynamic phonons in spin-Peierls compounds such as GeCuO3 and NaV2O5 must be included in order to obtain a correct quantitative description of their magnetic properties, both above and below the dimerization temperature.

A Customizable Camera-based Human Computer Interaction System Allowing People With Disabilities Autonomous Hands Free Navigation of Multiple Computing Task

Many people suffer from conditions that lead to deterioration of motor control and makes access to the computer using traditional input devices difficult. In particular, they may loose control of hand movement to the extent that the standard mouse cannot be used as a pointing device. Most current alternatives use markers or specialized hardware to track and translate a user's movement to pointer movement. These approaches may be perceived as intrusive, for example, wearable devices. Camera-based assistive systems that use visual tracking of features on the user's body often require cumbersome manual adjustment. This paper introduces an enhanced computer vision based strategy where features, for example on a user's face, viewed through an inexpensive USB camera, are tracked and translated to pointer movement. The main contributions of this paper are (1) enhancing a video based interface with a mechanism for mapping feature movement to pointer movement, which allows users to navigate to all areas of the screen even with very limited physical movement, and (2) providing a customizable, hierarchical navigation framework for human computer interaction (HCI). This framework provides effective use of the vision-based interface system for accessing multiple applications in an autonomous setting. Experiments with several users show the effectiveness of the mapping strategy and its usage within the application framework as a practical tool for desktop users with disabilities.