visualization of biological macromolecules shuchismita dutta, ph.d
TRANSCRIPT
Visualization of Biological Macromolecules
Shuchismita Dutta, Ph.D.
Why Visualize?
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Visualization Objectives
• Understand the structural data• Visualize structural data (using software e.g. Chimera)
– Atomic model (using coordinates from PDB)– Maps (computed using experimental data from PDB)
• Analyze protein/nucleic acid structures– Select and display specific atoms/groups of atoms and
neighboring atoms/ligands– Draw hydrogen bonds– Measure distances/angles etc.
• Compare structures of related macromolecules • Create figures of molecular structures that tell a story
Evolution of Visualization
Jane Richardson
Hand-drawn ribbon diagram of Triosephosphate isomerasehttp://en.wikipedia.org/wiki/Jane_S._Richardson
http://www.wellcomecollection.org/full-image.aspx?page=1139&image=john-kendrew-and-maz-perutz
John Kendrew and Max Perutz looking at the “forest of rods” model of myoglobin
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Visualize molecules on a computer1. Coordinate file from PDB
2. Visualization softwareRasMol, Chimera, Swiss PDB Viewer etc.
3. Computer4. Molecule image
What is in the PDB?• Coordinate and experimental data files • Details about sample preparation, data collection and
structure solution• Sequence(s) of polymers (proteins and nucleic acids) in
the structure• Information about ligands in the structure
• Links to various resources that describe the sequence, function and other properties of the molecule.
• Classification of structures by sequence, structure, function and other criteria
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A Tour of the RCSB PDB web-siteDefault View
Exploring a Specific Structure (PDB ID 4hhb)
Exploring 4hhb – contd.
Header
Composition of Structure
Ligands
Polymer sequence
Secondary Structure and Links
Origin and Coordinates
Visualization Metaphors/Conventions
Spacefill
Wireframe Ribbons
What does a molecule look like?
All atoms Backbone
What to Show and How
Overlap of Gleevec &Sprycel bound to Abl kinase (PDB IDs 1iep, 2gqg)
Gleevec bound to Abl KinasePDB ID 1iep
Sprycel bound to Abl Kinase
PDB ID 2gqg
Mira PatelStudent 2008, 2009
Treating Chronic Myeloid Leukemia
Ligands
• Chemical Component Dictionary– access from RCSB
PDB websiteOR– from http://ligand-
expo.rcsb.org/
PNN: Penicillin G
Biological Assembly
Missing Pieces
ATP Synthase:PDB entries1c17, 1e79,2a7u, 1l2p
Illustrations from D. Goodsell
Split entries
NMR Ensemble Structures
Sugarcane Defensin 5 protein, PDB ID 2ksk
Structure ComparisonSequence based
• Sequences with greater than 30% identity usually have similar structure
Structure based
• Sequences with less than 30% similarity may also have similar structures
Pairwise structure alignment: jFATCAT - flexible
Pairwise sequence alignment: Smith-Waterman
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Learning to Use Chimera
• Upload file and Save file/image/session• Select
chain/residue/atoms/neighbors/sequence• Display, color atoms/ ribbons/ surface/ labels• Structure analysis –
• H-bonds• measure bond lengths
• Structure superposition• Making a movie
Visualization Summary
• Understand the structural data• Visualize (using software e.g. Chimera)
– Atomic model (using coordinates from PDB)– Maps (computed using experimental data from PDB)
• Analyze protein/nucleic acid structures– Select and display specific atoms/groups of atoms– Identify neighboring atoms/ligands– Measure distances/angles etc.
• Compare structures of related macromolecules • Create figures of molecular structures that tell a story
Telling a story with figures
• Selection – of atoms, residues, polymer chains• Color – to denote identity, mark groups etc. • Representation – suitable for main points being made• Orientation – to clearly show the point being made• Labels – to mark and explain• Legened – to explain what is being shown
Tell a Story: How Hemoglobin Works
Note the use of:• Scroll• Color• Representation• Orientation• Labels
Structure of Kir2.2. (A) Stereoview of a ribbon representation of the Kir2.2 tetramer from the side with the extracellular solution above. Four subunits of the channel are uniquely colored. Approximate boundaries of the lipid bilayer are shown as gray bars. (B) A close-up view of the pore-region of a single subunit (in ribbon representation) with the turret, pore helix and selectivity filter labeled. Side chains of residues E139, R149 and a pair of disulfide-bonded cysteines (C123 and C155) are shown as sticks and colored according to atom type: carbon, yellow; nitrogen, blue; oxygen, red; and sulfur, green. Ionized hydrogen bonds are indicated by dashed black lines. The region flanked by the two disulfide-bonded cysteines is colored orange. (C) Electron density (blue wire mesh, 2Fo-Fc, calculated from 50 to 3.1Å using phases from the final model and contoured at 1.0 σ) is shown for the side chains of E139 and R149 [sticks, colored the same scheme as in (B)] forming a salt bridge. (D and E) K+ selectivity filter of the Kir2.2 channel (D) compared with that of the Kv1.2-Kv2.1 paddle chimera channel [(E), PDB ID 2R9R]. For clarity, only two of the four subunits [sticks, colored with the same scheme as in (B)] are shown. K+ (green spheres), water molecules (cyan spheres), and hydrogen bonds between R149 and E139 (Kir, dashed black lines), or between D379, M380 and waters (Kv, dashed black lines) are shown.
Tao X, Avalos JL, Chen J, MacKinnon R., Science. 2009 Dec 18;326(5960):1668-74.
Use of Selection, Color, Orientation, Labels and Legends