Predicting multibody assembly of proteins

textThis thesis addresses the multi-body assembly (MBA) problem in the context of protein assemblies. [...] In this thesis, we chose the protein assembly domain because accurate and reliable computational modeling, simulation and prediction of such assemblies would clearly accelerate discoveries in understanding of the complexities of metabolic pathways, identifying the molecular basis for normal health and diseases, and in the designing of new drugs and other therapeutics. [...] [We developed] F²Dock (Fast Fourier Docking) which includes a multi-term function which includes both a statistical thermodynamic approximation of molecular free energy as well as several of knowledge-based terms. Parameters of the scoring model were learned based on a large set of positive/negative examples, and when tested on 176 protein complexes of various types, showed excellent accuracy in ranking correct configurations higher (F² Dock ranks the correcti solution as the top ranked one in 22/176 cases, which is better than other unsupervised prediction software on the same benchmark). Most of the protein-protein interaction scoring terms can be expressed as integrals over the occupied volume, boundary, or a set of discrete points (atom locations), of distance dependent decaying kernels. We developed a dynamic adaptive grid (DAG) data structure which computes smooth surface and volumetric representations of a protein complex in O(m log m) time, where m is the number of atoms assuming that the smallest feature size h is [theta](r[subscript max]) where r[subscript max] is the radius of the largest atom; updates in O(log m) time; and uses O(m)memory. We also developed the dynamic packing grids (DPG) data structure which supports quasi-constant time updates (O(log w)) and spherical neighborhood queries (O(log log w)), where w is the word-size in the RAM. DPG and DAG together results in O(k) time approximation of scoring terms where k << m is the size of the contact region between proteins. [...] [W]e consider the symmetric spherical shell assembly case, where multiple copies of identical proteins tile the surface of a sphere. Though this is a restricted subclass of MBA, it is an important one since it would accelerate development of drugs and antibodies to prevent viruses from forming capsids, which have such spherical symmetry in nature. We proved that it is possible to characterize the space of possible symmetric spherical layouts using a small number of representative local arrangements (called tiles), and their global configurations (tiling). We further show that the tilings, and the mapping of proteins to tilings on arbitrary sized shells is parameterized by 3 discrete parameters and 6 continuous degrees of freedom; and the 3 discrete DOF can be restricted to a constant number of cases if the size of the shell is known (in terms of the number of protein n). We also consider the case where a coarse model of the whole complex of proteins are available. We show that even when such coarse models do not show atomic positions, they can be sufficient to identify a general location for each protein and its neighbors, and thereby restricts the configurational space. We developed an iterative refinement search protocol that leverages such multi-resolution structural data to predict accurate high resolution model of protein complexes, and successfully applied the protocol to model gp120, a protein on the spike of HIV and currently the most feasible target for anti-HIV drug design.Computer Science

Methods for Real-time Visualization and Interaction with Landforms

This thesis presents methods to enrich data modeling and analysis in the geoscience domain with a particular focus on geomorphological applications. First, a short overview of the relevant characteristics of the used remote sensing data and basics of its processing and visualization are provided. Then, two new methods for the visualization of vector-based maps on digital elevation models (DEMs) are presented. The first method uses a texture-based approach that generates a texture from the input maps at runtime taking into account the current viewpoint. In contrast to that, the second method utilizes the stencil buffer to create a mask in image space that is then used to render the map on top of the DEM. A particular challenge in this context is posed by the view-dependent level-of-detail representation of the terrain geometry. After suitable visualization methods for vector-based maps have been investigated, two landform mapping tools for the interactive generation of such maps are presented. The user can carry out the mapping directly on the textured digital elevation model and thus benefit from the 3D visualization of the relief. Additionally, semi-automatic image segmentation techniques are applied in order to reduce the amount of user interaction required and thus make the mapping process more efficient and convenient. The challenge in the adaption of the methods lies in the transfer of the algorithms to the quadtree representation of the data and in the application of out-of-core and hierarchical methods to ensure interactive performance. Although high-resolution remote sensing data are often available today, their effective resolution at steep slopes is rather low due to the oblique acquisition angle. For this reason, remote sensing data are suitable to only a limited extent for visualization as well as landform mapping purposes. To provide an easy way to supply additional imagery, an algorithm for registering uncalibrated photos to a textured digital elevation model is presented. A particular challenge in registering the images is posed by large variations in the photos concerning resolution, lighting conditions, seasonal changes, etc. The registered photos can be used to increase the visual quality of the textured DEM, in particular at steep slopes. To this end, a method is presented that combines several georegistered photos to textures for the DEM. The difficulty in this compositing process is to create a consistent appearance and avoid visible seams between the photos. In addition to that, the photos also provide valuable means to improve landform mapping. To this end, an extension of the landform mapping methods is presented that allows the utilization of the registered photos during mapping. This way, a detailed and exact mapping becomes feasible even at steep slopes

View generated database

This document represents the final report for the View Generated Database (VGD) project, NAS7-1066. It documents the work done on the project up to the point at which all project work was terminated due to lack of project funds. The VGD was to provide the capability to accurately represent any real-world object or scene as a computer model. Such models include both an accurate spatial/geometric representation of surfaces of the object or scene, as well as any surface detail present on the object. Applications of such models are numerous, including acquisition and maintenance of work models for tele-autonomous systems, generation of accurate 3-D geometric/photometric models for various 3-D vision systems, and graphical models for realistic rendering of 3-D scenes via computer graphics

Efficient collision detection for real-time simulated environments

Thesis (M.S.)--Massachusetts Institute of Technology, Program in Media Arts & Sciences, 1994.Includes bibliographical references (leaves 64-68).by Paul Jay Dworkin.M.S

Advances in Robot Navigation

Robot navigation includes different interrelated activities such as perception - obtaining and interpreting sensory information; exploration - the strategy that guides the robot to select the next direction to go; mapping - the construction of a spatial representation by using the sensory information perceived; localization - the strategy to estimate the robot position within the spatial map; path planning - the strategy to find a path towards a goal location being optimal or not; and path execution, where motor actions are determined and adapted to environmental changes. This book integrates results from the research work of authors all over the world, addressing the abovementioned activities and analyzing the critical implications of dealing with dynamic environments. Different solutions providing adaptive navigation are taken from nature inspiration, and diverse applications are described in the context of an important field of study: social robotics

Part decomposition of 3D surfaces

This dissertation describes a general algorithm that automatically decomposes realworld scenes and objects into visual parts. The input to the algorithm is a 3 D triangle mesh that approximates the surfaces of a scene or object. This geometric mesh completely specifies the shape of interest. The output of the algorithm is a set of boundary contours that dissect the mesh into parts where these parts agree with human perception. In this algorithm, shape alone defines the location of a bom1dary contour for a part. The algorithm leverages a human vision theory known as the minima rule that states that human visual perception tends to decompose shapes into parts along lines of negative curvature minima. Specifically, the minima rule governs the location of part boundaries, and as a result the algorithm is known as the Minima Rule Algorithm. Previous computer vision methods have attempted to implement this rule but have used pseudo measures of surface curvature. Thus, these prior methods are not true implementations of the rule. The Minima Rule Algorithm is a three step process that consists of curvature estimation, mesh segmentation, and quality evaluation. These steps have led to three novel algorithms known as Normal Vector Voting, Fast Marching Watersheds, and Part Saliency Metric, respectively. For each algorithm, this dissertation presents both the supporting theory and experimental results. The results demonstrate the effectiveness of the algorithm using both synthetic and real data and include comparisons with previous methods from the research literature. Finally, the dissertation concludes with a summary of the contributions to the state of the art