ABSTRACT
Macromolecules such as proteins and enzymes are responsible for most of cellular functionality. Many molecular interactions, such as protein-protein interactions or protein-ligand binding, occur at what can be defined as the molecular surface. The topology of the molecular surface is often complex, containing various geometric features such as clefts, cavities, tunnels, and flat regions. These geometric features coupled with non-geometric physicochemical properties influence surface-based molecular interactions. Consequently analysis of molecular surfaces is crucial in elucidating structure-property relationships of molecules. In this paper we propose a method for visualizing a molecular surface in a manner that preserves and elucidates salient features. The method involves mapping of a molecular surface to a standard spherical coordinate system. The ability to map arbitrary molecular surfaces to a standard coordinate system aids in comparison of surface features across different molecules. The mapping is accomplished by enclosing the molecular surface by a sphere, and then iteratively deforming the sphere until it converges by wrapping the entire molecular surface. This allows a one-to-one relationship to be established between points on the molecular surface and points on the surface of the sphere. The presence of discontinuities such as tunnels in the molecular surface can be identified by detecting collision between patches of the deforming sphere. Subsequently, the deformable surface is restored back to the sphere, retaining the mapping. Features and properties defined at the molecular surface are then mapped and visualized in the standard spherical coordinate system. The proposed approach has several key advantages. First, it allows a global-to-local visualization of molecular surfaces. Second, it facilitates comparison of specific features as well as collection of features within and across molecules by mapping them to a common coordinate system. Third, the method allows visualization of both geometric and non-geometric surface properties. Fourth, specific molecular characteristics can be visualized individually or in combination on-demand. Finally, and crucially the advantages offered by the proposed visualization do not involve simplification of the surface characteristics thereby ensuring that no loss of potentially important information occurs.
- N. A. Baker, D. Sept, S. Joseph, M. J. Holst, and J. A. McCammon. Electrostatics of nanosystems: application to microtubules and the ribosome. Proc. National Academy of Sciences, 98(18): 10037--10041, Aug 2001.Google ScholarCross Ref
- H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, P. E. Bourne: The Protein Data Bank, Nucleic Acids Research, 28 pp. 235--242 (2000).Google ScholarCross Ref
- A. T. Binkowski, L. Adamian, and J. Liang, "Inferring functional relationships of proteins from local sequence and spatial surface patterns", J. Mol. Biol., 2003, 332: 505--526Google ScholarCross Ref
- J. F. Blinn, "Simulation of Wrinkled Surfaces", Computer Graphics, Vol. 12 (3), pp. 286--292 SIGGRAPH-ACM (August 1978) Google ScholarDigital Library
- G. Cipriano and M. Gleicher, 2007. Molecular Surface Abstraction. IEEE Transactions on Visualization and Computer Graphics 13, 6 (Nov. 2007), 1608--1615. Google ScholarDigital Library
- M. L. Connolly, Analytical molecular surface calculation. Applied Crystallography 16 (1983), 548--558.Google ScholarCross Ref
- F. Ferre et al., "SURFACE: a database of protein surface regions for functional annotation", Nucleic Acids Research, 2004, Vol 32: D240--D244Google ScholarCross Ref
- T. Goddard, C. Huang, and T. Ferrin, "Software Extensions to UCSF Chimera for Interactive Visualization of Large Molecular Assemblies", Structure 13: 473--482, 2005Google ScholarCross Ref
- B. Huang and M. Schroeder, "Ligsite: Predicting Ligand Binding Sites Using the Connolly Surface and Degree of Conservation", BMC Structural Biology, 6: 19, 2006Google Scholar
- Jmol: an open-source Java viewer for chemical structures in 3D. http://www.jmol.org/Google Scholar
- M. Kass, A. Witkin, and D. Terzopoulos, "Snakes - Active Contour Models" International Journal of Computer Vision, 1(4): 321--331, 1987.Google ScholarCross Ref
- R. A. Laskowski, SURFNET: A Program for Visualizing Molecular Surfaces, Cavities, and Intermolecular Interactions. J. Mol. Graph., 13: 323--330, 1995.Google ScholarCross Ref
- B. Li et al. "Characterization of local geometry of protein surfaces with the visibility criterion", Proteins 71: 670--683, 2008Google ScholarCross Ref
- J Liang, H. Edelsbrunner, C. Woodward, "Anatomy of Protein Pockets and Cavities: Measurement of Binding Site Geometry and Implications for Ligand Design", Protein Sci, 7: 1884--1897, 1998Google ScholarCross Ref
- T. McInerney and D. Terzopolous. A Dynamic Finite Element Surface Model for Segmentation and Tracking in Multidimensional Medical Images with Application to Cardiac 4D Image Analysis. Comput Med Imag Graph, vol. 19, pp. 69--83, 1995.Google ScholarCross Ref
- K. Pawlowski and A. Godzik, "Surface Map Comparison: studying Function Diversity of Homologous Proteins", J. Mol. Biol., 2001, 309: 793--806Google ScholarCross Ref
- F. M. Richards, "Areas, volumes, packing and protein structure," Annual Review of Biophysics and Bioengineering, 6, 1977, pp. 151--76.Google ScholarCross Ref
- R. Singh, Surface Similarity-Based Molecular Query-Retrieval, BMC Cell-Biology, Vol. 8, Suppl. 1 (S6): July, 2007Google Scholar
- M. Sanner, "A Component-Based Software Environment for Visualizing Large Macromolecular Assemblies", Structure 3(3): 447--462, 2005Google ScholarCross Ref
- J. Sasin, A. Godzik, and J. Bujnicki, "Surf's Up! -- Protein Classification by Surface Comparison", J. Biosci., 32(1), pp 97--100, 2007Google ScholarCross Ref
- S. Schmitt, D. Kuhn, and G. Klebe, "A new method to detect related function among proteins independent of sequence and fold homology", J. Mol. Biol., 2002, 323: 387--406.Google ScholarCross Ref
- Y. Tsuchiya, K. Kinoshita, and H. Nakamura, "Structure-based prediction of DNA-binding sites on proteins using the empirical preference of electrostatic potential and the shape of molecular surfaces", PROTEINS: structure, Function, and Bioinformatics 55: 885--894, 2004Google ScholarCross Ref
- X. Zhang and C. Bajaj, "Extraction, Visualization and Quantification of Protein Pockets", Proceeding of 6th annual International Conference on Computational System Bioinformatics Conference (CSB 2007), p. 275--286, San Diego, CA, 2007.Google Scholar
Index Terms
- Global-to-local representation and visualization of molecular surfaces using deformable models
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