Visualization of
Macromolecular Structures
Shuchismita Dutta
Molecules Around You
Julian Voss-Andreae
David Goodsell
Why Visualize?
• Communication: since human eye effective
in pattern recognition
• Summarize information
– what, where, how many (data)?
– mechanisms
– change (cause and effect)
• Decision making aid
Visual storytelling
Road sign near Niagara Falls. Picture postedby Tim Roy
http://dd.dynamicdiagrams.com/?p=541
Story: How Hemoglobin Works
What, Where, How Many?
http://popvssoda.com:2998/
What, Where, How Many?
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.
Change and Mechanism
Figure 1
Crystal structure of SNARE-induced Ca2+-bound Syt3. (a) Showing a ribbon diagram of the C2AB fragment of Syt3 including the C2A (magenta) and C2B (yellow)
domains, and bound Ca2+ ions (gray spheres). (b) Side view illustrating that the Ca2+-binding loops of both C2 domains emerge from the same side of the molecule.
Residues Lys427, Lys557, and Arg556 are shown as sticks. (c) Superposition of the crystal structures of SNARE-induced Ca2−-bound (magenta and yellow) and Ca2+free (blue, PDB ID 1DQV20) Syt3 C2AB fragments. We aligned structures by superposition of the Cα positions of their respective C2A domains (see cartoon where the
“+” sign indicates the Ca2+-binding regions).
Vrljic M, Strop P, Ernst JA, Sutton RB, Chu S, Brunger AT. Nat Struct Mol Biol. 2010, 17(3): 325–331.
Decision Making Aid
Treating Chronic Myeloid Leukemia
T315I
Gleevec
bound to Abl Kinase
PDB ID 1iep
GLEEVEC
F317L
SPRYCEL
Mira Patel
Student 2008, 2009
Phosphate Binding Loop
Sprycel
bound to Abl Kinase
PDB ID 2gqg
Activation Loop
Overlap of Gleevec &
Sprycel bound to
Abl kinase
(PDB IDs 1iep, 2gqg)
Visualization
http://www.umass.edu/microbio/rasmol/history.htm
Early Drawings of Molecules
Roger Hayward
Linus Pauling
Irving Geis
Richard Dickerson
www.umass.edu/microbio/rasmol/history.htm
Toobers
Rapid prototyping
Laser crystal
Wire models (1958)
Richard’s box (1958)
Ball and Spoke (1960)
Byron’s bender (1970s)
Rapid prototyping (1990s)
Toobers (2000s)
Byron’s bender
Physical Models
Computer Models
Early computers (1960s-70s)
TAMS (1980s)
Evans & Sutherland (1980s-90s)
Modern computers (1990s …)
Kinemage, Rasmol, Chimera …
Ribbons
Wireframe
Ball and Stick
Space fill
Surface
Visualizing Molecules
• Visual Metaphors
– assumptions and conventions
• Dealing with Coordinates
– Biological assembly
– Missing atoms/residues
– Split entries
• Aesthetic Choices
– Use of orientation, color and style
• Scale: Atoms to Cells
Visualization Metaphors
What does a molecule look like?
Wireframe
Ribbons
Backbone
All atoms
Spacefill
Style and Purpose
• Overall shape & structure – space fill
• Fold, classification etc. - ribbons
• Biologically significant regions - ball & stick, stick
– Understand binding geometry
– Design activators, inhibitors, drugs
• Because molecules are complex and beautiful – mixed
or other creative representations
Illustrations from D. Goodsell
Dealing with Coordinates:
Biological Assembly
Dealing with Coordinates: Missing Pieces
ATP Synthase:
PDB entries
1c17, 1e79,
2a7u, 1l2p
Illustrations from D. Goodsell
Dealing with Coordinates: Split entries
Program Defaults
Waters?
Aesthetic Choices
• Orientation
• Color
• Style
PDB ID 1tim
chain B
Scale: Atoms to Molecules to Cells
Illustrations from D. Goodsell
Illustrations that span scales from nanometers to microns,
for use in education and science outreach.
Visualize molecules on a computer
1. Coordinate file from PDB
4. Molecule image
3. Computer
2. Visualization software
RasMol, Chimera,
Swiss PDB Viewer etc.
PDB Format File: a Database Report
• The database is built on PDB exchange &
chemical component dictionaries which helps
with keeping track of all the information
• Validation uses dictionaries to
– Check inter-relationships between different data
components (PDB exchange dictionary)
– Match information to chemical component
dictionary
Exploring PDB file
Meta data
Coordinates
Title section
OBSLTE 18-JUL-84 1HHB 2HHB 3HHB 4HHB
SPLIT 1JGP 1JGQ 1JGO
CAVEAT 1B86 THERE ARE CHIRALITY ERRORS IN C-ALPHA CENTERS
REVDAT
REVDAT
REVDAT
REVDAT
4
3
2
1
24-FEB-09
01-APR-03
15-OCT-89
17-JUL-84
4HHB
4HHB
4HHB
4HHB
1 VERSN
1 JRNL
3 MTRIX
0
SPRSDE 17-JUL-84 4HHB 1HHB
Remarks: the numbers mean
something
Biological assembly information
Example of a virus (1AYN)
Remarks
Compound details
Missing residues, atoms
Geometry: close contacts, bond length, angle and
torsion deviations, sterochemistry
Ligand details
Related entries
Sequence details
Chemistry sections :
Primary Structure & Ligand
DBREF 1BH0 A 1 29 UNP P01275 GLUC_HUMAN 53 81
SEQADV 1BH0 LYS A 17 UNP P01275 ARG 69 ENGINEERED
SEQADV 1BH0 LYS A 18 UNP P01275 ARG 70 ENGINEERED
SEQADV 1BH0 GLU A 21 UNP P01275 ASP 73 ENGINEERED
SEQRES 1 A 29 HIS SER GLN GLY THR PHE THR SER ASP TYR SER LYS TYR
SEQRES 2 A 29 LEU ASP SER LYS LYS ALA GLN GLU PHE VAL GLN TRP LEU
SEQRES 3 A 29 MET ASN THR
MODRES 2F4K NLE A 65 LEU NORLEUCINE
MODRES 2F4K NLE A 70 LEU NORLEUCINE
HET PO4 D 147 1
HET PO4 B 147 1
HET HEM A 142 43
HET HEM B 148 43
HET HEM C 142 43
HET HEM D 148 43
HETNAM PO4 PHOSPHATE ION
HETNAM HEM PROTOPORPHYRIN IX CONTAINING FE
HETSYN HEM HEME
FORMUL 5 PO4 2(O4 P 3-)
FORMUL 7 HEM 4(C34 H32 FE N4 O4)
FORMUL 11 HOH *221(H2 O)
Secondary Structure & Connectivity
HELIX 1 AA SER A 3 GLY A 18 1 16
HELIX 2 AB HIS A 20 SER A 35 1 16
HELIX 3 AC PHE A 36 TYR A 42 1 7
SHEET 1 A 4 ILE A 18 LEU A 23 0
SHEET 2 A 4 LEU A 111 VAL A 118 -1 O GLY A 115 N TRP A 19
SSBOND
SSBOND
SSBOND
SSBOND
LINK
LINK
LINK
LINK
1
2
3
4
CYS
CYS
CYS
CYS
A
A
A
A
6
30
64
76
NE2 HIS A 87
NE2 HIS B 92
FE HEM B 147
FE HEM A 143
CYS
CYS
CYS
CYS
FE
FE
O1
O1
A
A
A
A
HEM
HEM
OXY
OXY
127 1555 1555 2.02
115 1555 1555 2.02
80 1555 1555 2.03
94
1555 1555 2.01
A
B
B
A
143
147
150
150
1555
1555
1555
1555
CISPEP 1 PRO A 98 PRO A 99 0 0.53
CISPEP 2 GLY A 109 PRO A 110 0 -0.01
1555
1555
1555
1555
1.94
2.07
1.87
1.66
Crystallographic info, Coordinate
Transformations & coordinates
CRYST1 88.814 95.207 89.164 90.00 104.96 90.00 P 1 21 1 8
ORIGX1 1.000000 0.000000 0.000000 0.00000
ORIGX2 0.000000 1.000000 0.000000 0.00000
ORIGX3 0.000000 0.000000 1.000000 0.00000
SCALE1 0.011259 0.000000 0.003009 0.00000
SCALE2 0.000000 0.010503 0.000000 0.00000
SCALE3 0.000000 0.000000 0.011609 0.00000
MODEL 1
ATOM 1 N
ATOM 2 CA
ATOM 3 C
ATOM 4 O
ATOM 5 CB
ATOM 6 OG
ATOM 7 N
ATOM 8 CA
...
ENDMDL
SER
SER
SER
SER
SER
SER
THR
THR
A
A
A
A
A
A
A
A
41
41
41
41
41
41
42
42
-9.122
-8.282
-7.051
-6.646
-7.845
-7.250
-6.473
-5.290
-10.304
-11.187
-11.693
-11.108
-10.416
-11.264
-12.792
-13.380
89.511
88.650
89.414
90.421
87.393
86.423
88.935
89.552
0.12
0.12
0.12
0.12
0.12
0.12
0.12
0.12
51.94
52.75
52.51
53.15
51.93
52.59
51.75
50.38
N
C
C
O
C
O
N
C
GLY
GLY
GLY
GLY
GLY
GLY
GLY
GLY
ASER
ASER
ASER
ASER
ASER
ASER
BGLY
BGLY
BGLY
BGLY
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
8
8
8
8
9
9
9
9
10
10
10
10
10
10
10
10
10
10
2.326
3.121
3.533
4.302
3.080
3.330
4.552
4.720
5.404
6.598
6.236
5.150
7.516
8.894
5.404
6.598
6.236
5.150
4.110
3.079
3.408
2.642
4.526
4.880
5.685
6.098
6.014
6.814
8.234
8.733
6.864
6.884
6.014
6.814
8.234
8.733
1.416
2.065
3.476
4.092
4.038
5.396
5.709
6.885
4.753
5.042
5.479
5.233
3.822
4.237
4.753
5.042
5.479
5.233
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
0.33
0.33
0.33
0.33
0.33
0.33
0.67
0.67
0.67
0.67
Microheterogeneity (1ENM)
42.03
42.27
42.32
44.09
40.18
40.11
39.75
40.96
39.21
38.11
36.87
32.77
39.46
40.79
39.21
38.11
36.87
32.77
Atom type
B-factor
Occupancy
z coordinate
y coordinate
x coordinate
Residue #
N
CA
C
O
N
CA
C
O
N
CA
C
O
CB
OG
N
CA
C
O
Chain ID
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
Residue name
Atom name
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
Alternate conformer ID
ATOM
ATOM
ATOM
ATOM
S.#
Coordinate section: A Closer look
N
C
C
O
N
C
C
O
N
C
C
O
C
O
N
C
C
O
1 N
2 CA
3 C
4 O
5 CB
6 N
7 CA
8 C
9 O
10 CB
11 N
12 CA
13 C
14 O
15 CB
16 CG
17 OD1
18 OD2
19 N
20 CA
21 C
22 O
GLU
GLU
GLU
GLU
GLU
ALA
ALA
ALA
ALA
ALA
ASP
ASP
ASP
ASP
ASP
ASP
ASP
ASP
CYS
CYS
CYS
CYS
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
1C
1C
1C
1C
1C
1B
1B
1B
1B
1B
1A
1A
1A
1A
1A
1A
1A
1A
1
1
1
1
63.677
64.338
63.351
63.320
65.320
62.537
61.571
60.631
60.238
60.810
60.262
59.378
57.965
57.476
59.593
58.724
57.452
59.188
57.321
56.005
55.351
56.002
26.331
26.818
27.360
28.565
25.825
26.499
26.988
28.018
27.865
25.845
29.089
30.016
29.526
28.873
31.557
32.268
32.455
32.658
29.802
29.353
30.160
30.636
17.947
16.736
15.717
15.489
16.101
15.096
14.116
14.729
15.872
13.511
14.012
14.691
14.760
13.851
14.587
13.564
13.924
12.472
15.860
16.036
17.077
17.968
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
Residue numbering (1DWD)
31.77
35.78
41.73
49.37
38.64
36.03
33.01
32.42
31.68
33.36
33.13
35.05
31.74
36.72
41.32
46.17
47.60
48.99
22.52
15.35
15.83
18.73
Atom type
B-factor
Occupancy
z coordinate
y coordinate
x coordinate
Chain ID
Residue #
Residue name
Atom name
S.#
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
Insertion codes
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
N
C
C
O
C
N
C
C
O
C
N
C
C
O
C
C
O
O
N
C
C
O
www.wwpdb.org
mmCIF format file
-snip-
PDB format file
PDB Format vs mmCIF Format
• 80 characters wide
• Includes header and
coordinates (x, y, z,
occupancy and B-factors) for
all atoms.
• Includes name, source and
sequence of all polymers
• Can include a maximum of
62 chains and 99999 atoms.
• Free format
• Includes header and
coordinates (x, y, z,
occupancy and B-factors) for
all atoms.
• Includes name, source and
sequence of all polymers
• No restriction to number of
chains or atoms in file.
Dictionaries
• PDB Exchange (pdbx) dictionary
– (http://mmcif.pdb.org/)
– Includes the syntax, definitions, relations, boundaries
– Includes examples for the contents of the mmCIF format
file.
• Chemical Component Dictionary
– Describes all residues in the PDB files (standard, nonstandard amino acids, nucleotides and other ligands - ions,
drugs, cofactors, inhibitors)
– 1-3 alphanumeric character identifier
– Includes model & idealized coordinates for components,
connectivities, name, formula, smiles strings
– Maintained by the wwPDB.
– Used for data processing and validation of structures
PDB Exchange
Dictionary
includes syntax &
definitions for
mmCIF format
files
PDB format file
mmCIF format file
-snip-
Instance of valine
matched to VAL in
Chemical Component
Dictionary
Visualization software
•
•
•
•
•
•
•
•
RasMol
Chimera
Pymol
Jmol
Webmol
King
Cn3D
MolMol
•
•
•
•
Swiss PDB viewer
MolView
MIDAS
VMD
Using Chimera Checklist
• Upload file and Save file/image/session
• Select chain/residue/atoms/neighbors
• Display (and color) atoms/ ribbons/ surface/
labels
• Structure analysis – measure bond lengths,
angles