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Structure Visualization Boris Steipe University of Toronto [email protected] 3.4 1 Visualizations: abstractions to aid understanding CPK 3.4 Line Trace Cartoon 2 Visualization of 3D relationships requires stereo vision 1CDL.PDB • Practice regularily • Increase image size • Increase viewing distance • Increase complexity 3.4 set stereo -5 select protein color chain select *.ca and hetero color [0,180,255] select within (3.0, (*.ca and hetero)) and *.O* color red 3 Global features of structure quarternary structure global fold machine metaphore, mimicry interfaces surprising structural similarity homology unusual surface and core residues location of SNPs or sites and context of mutations, PTM sites 3.4 residues that participate in ligand binding conformational changes molecular mechanisms shape clefts, pockets, protrusions 4 Distances in protein structure Size Hydrogen bonds Bond-lengths Binding sites Rasmol: set 3.4 picking distance Salt-bridges 5 Distances from coordinates XYZ coordinates are vectors in an orthogonal coordinate system, in Å. All the rules of analytical geometry apply. [...] ATOM [...] ATOM [...] d = = = = = 3.4 687 OH TYR 86 7.415 62.584 32.900 1.00 3.37 651 O ASP 82 9.996 62.571 32.488 1.00 5.18 [(9.996-7.415)2 + (62.571-62.584)2 + (32.488-32.900)2]0.5 [(2.581)2 + (-0.013)2 + (-0.412)2]0.5 [6.661561 + 0.0000169 + 0.169744]0.5 [6.831474]0.5 2.614 Å = 0.2614 nm = 2.614 . 10-10 m 6 Distances and angles: Ligand binding H-bonds have specific geometric requirements with respect to distance and angles. They confer conformational specificity to proteins. More than 90% of Hbond "valences" are usually satisfied and geometries cluster closely around consensus distances and angles. ±30° Chelation: Calcium bound in Calmodulin (1CLL.PDB) D ±70° H A 2.85±0.25 Å (Hydrogen coordinates are usually inferred !) 3.4 7 Dihedral angles i+3 Single bonds: Freely rotable, but constrained by steric overlap. i Double bonds: Constrained to planar geometry. Large energetic barrier to isomerization. i+2 i+1 +f Rasmol: set 3.4 picking torsion 8 Backbone dihedral angles: Ramachandran plots f 3.4 9 Sidechain rotamers 3 2 100 randomly chosen Phe-residues superimposed. Ponder & Richards (1987) J. Mol. Biol. 193, 775-791 http://www.fccc.edu/research/labs/dunbrack/sidechain.html 3.4 10 B-factors B-factors are isotropic temperature factors, i.e. they model the relationship between observed and theoretical electron density of an atom at rest by applying a spherically symmetrical thermal distribution to the density until it best matches the experiment. "Real" devitions from ideality are neither isotropic nor thermally distributed, they can correspond to discrete disorder, dynamic mobility and will be influenced by experimental error of measurement and refinement problems. 3.4 2IMM.PDB: Rasmol, CPK, color by temperature, slab mode. 11 Molecular complementarity Tyr H33 Arg H52 Tyr L100 Tight and specific binding implies that all features of the ligand will be recognized by the protein. Trp H107 negative charge hydrophilic Asp L97 hydrophobic Phosphorylcholine in antibody binding site (2MCP.PDB) 3.4 positive charge 12 Mapping properties on surfaces • Properties of atoms (B-factors) • Ensemble properties of residues (hydrophobicity, conservation) • Geometry (local curvature) • Fields and potentials (isosurfaces, binding potential) AChE (1ACL.PDB) color coded by electrostatic potential with GRASP. http://trantor.bioc.columbia. edu/grasp/ 3.4 13 Visualization tools ORTEP 3.4 Rasmol Chime MolMol Cn3D others Molscript .... POVRay 14 Tools • • • • 3.4 RasMol Cn3D DeepView VMD 15 RasMol Small footprint, easy to install, sufficient functionality for most tasks, widely distributed, powerful commandline interface, scriptable. Work through the Rasmol tutorial ! http://biochemistry.utoronto.ca/steipe/bioinformatics • Rasmol download • Features • Stereo vision ! L R 1DRO.PDB, model 1 3.4 16 Cn3D Good integration with NCBI databases, excellent functionality for domain and conservation analysis. Scriptable. No stereo :-( Work through the Cn3D tutorial ! http://ncbi.nih.gov/Structure/CN3D/cn3dtut.shtml 3.4 17 DeepView (Swiss PDB Viewer) Excellent tool for homology modeling, structure manipulation, structure alignment and analysis of sequence alignments. Calculates surfaces and electrostatics. Creates PovRay scenes. Good integration with SwissModel. Work through either DeepView tutorial ! http://ca.expasy.org/spdbv/text/tutorial.htm http://www.usm.maine.edu/~rhodes/SPVTut/ 3.4 18 VMD (http://www.ks.uiuc.edu/Research/vmd/) Very powerful, well maintained, good graphics, intuitive use, scriptable and well integrated with NAMD. Work through the VMD tutorial ! http://www.ks.uiuc.edu/Research/vmd/vmd-1.8.2/tutorial/html/vmd-tutorial.html 3.4 19