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.

Search by Shape Examples: Modeling Nonrigid Deformation

We describe our work on shape-based image database search using the technique of modal matching. Modal matching employs a deformable shape decomposition that allows users to select example objects and have the computer efficiently sort the set of objects based on the similarity of their shape. Shapes are compared in terms of the types of nonrigid deformations (differences) that relate them. The modal decomposition provides deformation "control knobs" for flexible matching and thus allows for selecting weighted subsets of shape parameters that are deemed significant for a particular category or context. We demonstrate the utility of this approach for shape comparison in 2-D image databases; however, the general formulation is applicable to signals of any dimensionality.

On the Effectiveness of Genetic Search in Combinatorial Optimization

In this paper, we study the efficacy of genetic algorithms in the context of combinatorial optimization. In particular, we isolate the effects of cross-over, treated as the central component of genetic search. We show that for problems of nontrivial size and difficulty, the contribution of cross-over search is marginal, both synergistically when run in conjunction with mutation and selection, or when run with selection alone, the reference point being the search procedure consisting of just mutation and selection. The latter can be viewed as another manifestation of the Metropolis process. Considering the high computational cost of maintaining a population to facilitate cross-over search, its marginal benefit renders genetic search inferior to its singleton-population counterpart, the Metropolis process, and by extension, simulated annealing. This is further compounded by the fact that many problems arising in practice may inherently require a large number of state transitions for a near-optimal solution to be found, making genetic search infeasible given the high cost of computing a single iteration in the enlarged state-space.

Stochastic Mesh-Based Multiview Reconstruction

A method for reconstruction of 3D polygonal models from multiple views is presented. The method uses sampling techniques to construct a texture-mapped semi-regular polygonal mesh of the object in question. Given a set of views and segmentation of the object in each view, constructive solid geometry is used to build a visual hull from silhouette prisms. The resulting polygonal mesh is simplified and subdivided to produce a semi-regular mesh. Regions of model fit inaccuracy are found by projecting the reference images onto the mesh from different views. The resulting error images for each view are used to compute a probability density function, and several points are sampled from it. Along the epipolar lines corresponding to these sampled points, photometric consistency is evaluated. The mesh surface is then pulled towards the regions of higher photometric consistency using free-form deformations. This sampling-based approach produces a photometrically consistent solution in much less time than possible with previous multi-view algorithms given arbitrary camera placement.

Stochastic Refinement of the Visual Hull to Satisfy Photometric and Silhouette Consistency Constraints

An iterative method for reconstructing a 3D polygonal mesh and color texture map from multiple views of an object is presented. In each iteration, the method first estimates a texture map given the current shape estimate. The texture map and its associated residual error image are obtained via maximum a posteriori estimation and reprojection of the multiple views into texture space. Next, the surface shape is adjusted to minimize residual error in texture space. The surface is deformed towards a photometrically-consistent solution via a series of 1D epipolar searches at randomly selected surface points. The texture space formulation has improved computational complexity over standard image-based error approaches, and allows computation of the reprojection error and uncertainty for any point on the surface. Moreover, shape adjustments can be constrained such that the recovered model's silhouette matches those of the input images. Experiments with real world imagery demonstrate the validity of the approach.

World Wide Web Image Search Engines

We propose the development of a world wide web image search engine that crawls the web collecting information about the images it finds, computes the appropriate image decompositions and indices, and stores this extracted information for searches based on image content. Indexing and searching images need not require solving the image understanding problem. Instead, the general approach should be to provide an arsenal of image decompositions and discriminants that can be precomputed for images. At search time, users can select a weighted subset of these decompositions to be used for computing image similarity measurements. While this approach avoids the search-time-dependent problem of labeling what is important in images, it still holds several important problems that require further research in the area of query by image content. We briefly explore some of these problems as they pertain to shape.

Image Digestion and Relevance Feedback in the ImageRover WWW Search Engine

ImageRover is a search by image content navigation tool for the world wide web. The staggering size of the WWW dictates certain strategies and algorithms for image collection, digestion, indexing, and user interface. This paper describes two key components of the ImageRover strategy: image digestion and relevance feedback. Image digestion occurs during image collection; robots digest the images they find, computing image decompositions and indices, and storing this extracted information in vector form for searches based on image content. Relevance feedback occurs during index search; users can iteratively guide the search through the selection of relevant examples. ImageRover employs a novel relevance feedback algorithm to determine the weighted combination of image similarity metrics appropriate for a particular query. ImageRover is available and running on the web site.

Indexing Distances in Large Graphs and Applications in Search Tasks

This thesis elaborates on the problem of preprocessing a large graph so that single-pair shortest-path queries can be answered quickly at runtime. Computing shortest paths is a well studied problem, but exact algorithms do not scale well to real-world huge graphs in applications that require very short response time. The focus is on approximate methods for distance estimation, in particular in landmarks-based distance indexing. This approach involves choosing some nodes as landmarks and computing (offline), for each node in the graph its embedding, i.e., the vector of its distances from all the landmarks. At runtime, when the distance between a pair of nodes is queried, it can be quickly estimated by combining the embeddings of the two nodes. Choosing optimal landmarks is shown to be hard and thus heuristic solutions are employed. Given a budget of memory for the index, which translates directly into a budget of landmarks, different landmark selection strategies can yield dramatically different results in terms of accuracy. A number of simple methods that scale well to large graphs are therefore developed and experimentally compared. The simplest methods choose central nodes of the graph, while the more elaborate ones select central nodes that are also far away from one another. The efficiency of the techniques presented in this thesis is tested experimentally using five different real world graphs with millions of edges; for a given accuracy, they require as much as 250 times less space than the current approach which considers selecting landmarks at random. Finally, they are applied in two important problems arising naturally in large-scale graphs, namely social search and community detection.

Search Space Reduction in QoS Routing

To provide real-time service or engineer constrained-based paths, networks require the underlying routing algorithm to be able to find low-cost paths that satisfy given Quality-of-Service (QoS) constraints. However, the problem of constrained shortest (least-cost) path routing is known to be NP-hard, and some heuristics have been proposed to find a near-optimal solution. However, these heuristics either impose relationships among the link metrics to reduce the complexity of the problem which may limit the general applicability of the heuristic, or are too costly in terms of execution time to be applicable to large networks. In this paper, we focus on solving the delay-constrained minimum-cost path problem, and present a fast algorithm to find a near-optimal solution. This algorithm, called DCCR (for Delay-Cost-Constrained Routing), is a variant of the k-shortest path algorithm. DCCR uses a new adaptive path weight function together with an additional constraint imposed on the path cost, to restrict the search space. Thus, DCCR can return a near-optimal solution in a very short time. Furthermore, we use the method proposed by Blokh and Gutin to further reduce the search space by using a tighter bound on path cost. This makes our algorithm more accurate and even faster. We call this improved algorithm SSR+DCCR (for Search Space Reduction+DCCR). Through extensive simulations, we confirm that SSR+DCCR performs very well compared to the optimal but very expensive solution.

MosaicShape: Stochastic Region Grouping with Shape Prior

A novel method that combines shape-based object recognition and image segmentation is proposed for shape retrieval from images. Given a shape prior represented in a multi-scale curvature form, the proposed method identifies the target objects in images by grouping oversegmented image regions. The problem is formulated in a unified probabilistic framework and solved by a stochastic Markov Chain Monte Carlo (MCMC) mechanism. By this means, object segmentation and recognition are accomplished simultaneously. Within each sampling move during the simulation process,probabilistic region grouping operations are influenced by both the image information and the shape similarity constraint. The latter constraint is measured by a partial shape matching process. A generalized parallel algorithm by Barbu and Zhu,combined with a large sampling jump and other implementation improvements, greatly speeds up the overall stochastic process. The proposed method supports the segmentation and recognition of multiple occluded objects in images. Experimental results are provided for both synthetic and real images.

View-Invariant Object Category Learning, Recognition, and Search: How Spatial and Object Attention Are Coordinated Using Surface-Based Attentional Shrouds

Air Force Office of Scientific Research (F49620-01-1-0397); National Science Foundation (SBE-0354378); Office of Naval Research (N00014-01-1-0624)

Cortical Dynamics of Contextually-Cued Attentive Visual Learning and Search: Spatial and Object Evidence Accumulation

How do humans use predictive contextual information to facilitate visual search? How are consistently paired scenic objects and positions learned and used to more efficiently guide search in familiar scenes? For example, a certain combination of objects can define a context for a kitchen and trigger a more efficient search for a typical object, such as a sink, in that context. A neural model, ARTSCENE Search, is developed to illustrate the neural mechanisms of such memory-based contextual learning and guidance, and to explain challenging behavioral data on positive/negative, spatial/object, and local/distant global cueing effects during visual search. The model proposes how global scene layout at a first glance rapidly forms a hypothesis about the target location. This hypothesis is then incrementally refined by enhancing target-like objects in space as a scene is scanned with saccadic eye movements. The model clarifies the functional roles of neuroanatomical, neurophysiological, and neuroimaging data in visual search for a desired goal object. In particular, the model simulates the interactive dynamics of spatial and object contextual cueing in the cortical What and Where streams starting from early visual areas through medial temporal lobe to prefrontal cortex. After learning, model dorsolateral prefrontal cortical cells (area 46) prime possible target locations in posterior parietal cortex based on goalmodulated percepts of spatial scene gist represented in parahippocampal cortex, whereas model ventral prefrontal cortical cells (area 47/12) prime possible target object representations in inferior temporal cortex based on the history of viewed objects represented in perirhinal cortex. The model hereby predicts how the cortical What and Where streams cooperate during scene perception, learning, and memory to accumulate evidence over time to drive efficient visual search of familiar scenes.

A Neural Theory of Visual Search: Recursive Attention to Segmentations and Surfaces

A neural theory is proposed in which visual search is accomplished by perceptual grouping and segregation, which occurs simultaneous across the visual field, and object recognition, which is restricted to a selected region of the field. The theory offers an alternative hypothesis to recently developed variations on Feature Integration Theory (Treisman, and Sato, 1991) and Guided Search Model (Wolfe, Cave, and Franzel, 1989). A neural architecture and search algorithm is specified that quantitatively explains a wide range of psychophysical search data (Wolfe, Cave, and Franzel, 1989; Cohen, and lvry, 1991; Mordkoff, Yantis, and Egeth, 1990; Treisman, and Sato, 1991).

A Neural Theory of Attentive Visual Search: Interactions of Boundary, Surface, Spatial, and Object Representations

Visual search data are given a unified quantitative explanation by a model of how spatial maps in the parietal cortex and object recognition categories in the inferotemporal cortex deploy attentional resources as they reciprocally interact with visual representations in the prestriate cortex. The model visual representations arc organized into multiple boundary and surface representations. Visual search in the model is initiated by organizing multiple items that lie within a given boundary or surface representation into a candidate search grouping. These items arc compared with object recognition categories to test for matches or mismatches. Mismatches can trigger deeper searches and recursive selection of new groupings until a target object io identified. This search model is algorithmically specified to quantitatively simulate search data using a single set of parameters, as well as to qualitatively explain a still larger data base, including data of Aks and Enns (1992), Bravo and Blake (1990), Chellazzi, Miller, Duncan, and Desimone (1993), Egeth, Viri, and Garbart (1984), Cohen and Ivry (1991), Enno and Rensink (1990), He and Nakayarna (1992), Humphreys, Quinlan, and Riddoch (1989), Mordkoff, Yantis, and Egeth (1990), Nakayama and Silverman (1986), Treisman and Gelade (1980), Treisman and Sato (1990), Wolfe, Cave, and Franzel (1989), and Wolfe and Friedman-Hill (1992). The model hereby provides an alternative to recent variations on the Feature Integration and Guided Search models, and grounds the analysis of visual search in neural models of preattentive vision, attentive object learning and categorization, and attentive spatial localization and orientation.