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Research

One of ProteinShop main contributions is the adaptation of inverse kinematics (IK) algorithms commonly used in robotics to implement an interactive manipulation feature that allows the user to select secondary structure segments i.e., alpha-helices and beta-strands-- and arrange them to form desired tertiary structures. ProteinShop's and POSE's IK translates 3-D motions into bond rotations, allowing users to manipulate proteins in an intuitive manner. Chemical bonds along the backbone between those segments are maintained during movement. Some of POSEs new capabilities are (1) energy visualization during manipulation to highlight regions of extraordinarily high energy, providing hints for where manipulations may be most effective or for how the energy and the gradient change during local optimization, (2) BuildBeta for fully automatic creation of low-energy beta-sheet configurations. These new features, described below, will be the core of our demonstration.

POSE computes and visualizes an energy function in real time and this capability may be used either to guide protein structure manipulation or to steer the docking process. POSE provides an interface for dynamically loading energy computation modules allowing users to couple different energy and scoring functions. Our program has two schemes for energy visualization, atom-based and volume-based. In the former, per-atom values can be visualized by mapping colors to atoms' van-der-Waals spheres. Volume rendering of energy produces a cleaner and more appealing representation than per-atom rendering because it reduces occlusion and visual clutter caused by van-der-Waals spheres. In addition, the program uses a color scheme to visualize individual energy components for a more detailed representation and understanding of the relationship between each energy component and the simulation being done.

BuildBeta is another new addition that increases POSEs ability to quickly create a variety of protein configurations. BuildBeta uses probability results on both protein fold topology [3] and sequence matching specificity [4] to automatically produce a high probability collection of possible initial sheet conformations. BuildBeta may work on the entire protein or on regions of a protein leaving a core part fixed. This feature may be useful in those cases in which protein structure predictors can determine the structure of a core part of a protein by homology with a known protein and they need to predict the position of the remaining beta strands outside the core. The current implementation of BuildBeta is limited to ten strands or less, which is the limit of Ruczinskis data fitting, and makes no attempt to make two or more sheets; all beta-strands are placed in one beta-sheet. We plan to extend multiple sheets from known cores using the multiple sheet scoring methods discussed in [5].

POSE supports exploratory steering of molecular docking. It permits the manipulation of multiple molecules with six degrees of freedom for each. Users may freely move the position and orientation of any molecule with respect to the others through pilot windows. When potential binding sites are known, the user can navigate a molecule to a binding site and experiment in real time the possible binding scenarios. POSE provides useful visual guides to assist users in the process. Examples of those guides include a transparent green sphere that highlights the area surrounding a potential hydrogen bond between molecules. The program constantly monitors the formation of intra- and inter-molecular hydrogen bonds displaying them with a dashed line. The length of a hydrogen bond, shown along the dashed line, is continuously updated during the interaction. Other visual guides include intermolecular collisions spheres that represent close contacts or atom collisions in real time.

Development

POSE is written in C++. The interface and graphical display unit are built using the FLTK toolkit while the rendering routines rely on OpenGL. Currently, POSE runs on any Unix/Linux compatible platform including Mac OS. 

Presentations and Demonstrations

"Protein Modeling with POSE: Protein Optimization Steering Environment"    [PDF]
Silvia Crivelli and Ting-Cheng Lu  ISMB Intelligent Systems for Molecular Biology 2005
"ProteinShop: a Tool for Interactive Protein Manipulation"
Silvia N. Crivelli, James Lu, James Lu, Oliver Kreylos, Nelson Max, and Wes Bethel 3Dsig: Structural Bioinformatics Meeting at ISMB 2004




Publications


References
1. http://www.cs.ucdavis.edu/~koehl/ProShape/