Tutorials for protein data
bank and swiss PDB viewer
2010/04/19
Prof. Jinn-Moon Yang
Yen-Fu Chen and Kai-Cheng Hsu
http://gemdock.life.nctu.edu.tw/dock/download/20100419_spv.ppt
http://gemdock.life.nctu.edu.tw/dock/download/20100419_spv.pdf
http://ppt.cc/cnqT (ppt)
http://ppt.cc/WWxd (pdf)
Contents
Introduction of protein structures
Using thymidine kinase as an example
Download and install
Tutorial
Download protein structures from PDB
Basic Operation
Advance Operation
Resources for tutorial
http://www.youtube.com/watch?v=yFE3CAHNkZg&feat
ure=related
Introduction of protein structures
Proteins present in all biological organisms
Polymers of amino acids (20 L-α-amino acids)
Nanoparticles
Perform particular biochemical functions
Transcription and translation
stemcells.nih.go: Early Development
Cell regulation and catalysis reactions
Nature: Mattson, M. Nature. 422, 385-387 (2003)
Introduction of protein structures
To enable to perform protein’s biological function, protein
fold into one or more specific spatial conformations driven by
noncovalent interactions
Hydrogen bonding, ionic interactions, van der Waals
forces and hydrophobic packing
3D protein structures are necessary for understanding the
functions of protein at molecular level
Protein structure: from amino acid to quaternary structure
Adapted from Protein Structure in Wikipedia
Hemoglobin: oxy-deoxy states
Adapted from structural biology Wikipedia
Noncovalent interactions for
protein structure and function
Ionic bond
A bond formed by the attraction between two oppositely
charged ions
Hydrogen bond
An attractive interaction of a hydrogen atom with an
electronegative atom, like N,O, and F
Potential energy of Na and Cl
Potential energy of Na and Cl
Noncovalent interactions for
protein structure and function
van der Waals force
Attractive or repulsive force between molecules
Hydrophobic interaction
The physical property of a molecule (known as a hydrophobe) that is
repelled from a mass of water
An example of van der Waals force:
Gecko climbs on the glass
An example of hydrophobic interaction:
Water drops on hydrophobic surface
Protein structure database:
Protein data bank (PDB)
Techniques for determining atomic structures
X-ray crystallography, NMR spectroscopy and
electron microscopy
PDB contains information about experimentallydetermined structures of biological marcomoleculeas
(proteins, and DNA/RNA)
Proteins (1kim)
X-ray
NMR
DNAs/RNAs (2k7e)
EM
http://www.pdb.org/
Biological complexes (1zrc)
Search protein structures in PDB
PDB provides search by protein name, ligand, or structrue
related keywords
Search example:
thymidine kinase (TK)
• Function: DNA synthesis
• Therapeutic: Anticancer and
antivirus drug target
Example: X-ray structures of virus’
thymidine kinase with substrates/inhibitors
Protein name
Source spices
Experimental method
has ligands
Search result of “X-ray structures of virus’
thymidine kinase with substrates/inhibitors”
23 structures for these keywords
PDB ID of
this structure
TK of virus
TK with ligand (substrate)
X-ray structure
Structure and related data (1kim)
Related data of
this structure
The title of this structure
The citation of this structure
Visualization
of biological
assembly
Structure and ligand data (1kim)
Ligand in this structure
Structure and sequence data
(1kim)
Related data of
this structure
Sequence ID of 1kim in
UniProtKB
Structure classification
ID of 1kim
Advance inspection for protein
structure: download structure from PDB
1. Save the data on your PC
2. Open the file on a structure
viewer program (swiss
PDBviewer, pymol, and etc.)
Classification of Drug Development
Unknown
O
O
High-Throughput Screening
(HTS)
O
O
Similar compounds
Structure-based Drug Design
(SBDD)
O
O
O
query
Known
Protein (receptor) Structure
Compound similarity search
SBDD or de novo design
O
Known
Compound structure
DDT 2002
Unknown
Discovering new leads
SBDD
HTS
Yellow: virtual screening (SBDD)
Blue: high-throughput screening (HTS)
•
•
•
•
There are more than 5 H-bond donors.
The molecular weight is over 500.
The LogP is over 5.
There are more than 10 H-bond acceptors.
Curr. opin. Chem. Biol. 2002, 439
Drugs derived from structure-based
approaches
Drug Discovery Today, 10, 895, 2005
Drug Discovery Today, 10, 895, 2005
Tutorial for Swiss PDB viewer
Download and install
Download Swiss PdbViewer
http://spdbv.vital-it.ch/download.html
Download user guide
http://spdbv.vital-it.ch/SwissPdbViewerManualv3.7.pdf
Tutorial video (English)
http://www.youtube.com/watch?v=nYT5qwtfNew&fe
ature=related
http://www.youtube.com/watch?v=yFE3CAHNkZg
Download page
General Terms
Main
chain
Residue
Arginine
Chain
Secondary
Structure (Ribbon)
Side chain
Gray: C atom
Blue: N atom
Red: O atom
Atom radius
A protein may have
multiple chains
Install and execute swiss pdb
viewer
Workspace
Layer info
Main window
Viewer
Control panel
Move & Rotate
Center
Zoom
Translate
Rotate
Open control panel
control panel
Load PDB1
Load PDB2
Display or hide residues
-for some residues
Press left button of mouse
Display or hide residues
-for all residues
Press right button of mouse
Display or hide side chains of
residues
Display or hide residue labels
GLU111
Display or hide atom radius
Render in solid 3D
Show secondary structures
-Display or hide ribbons
Bond length
1 angstrom (A) or 1 × 10−10 meters
1.52A
?A
Bond length
?A
Bond length
Hydrogen bond length
?A
Hydrogen bonds of helix
Hydrogen bond of helix
Hydrogen bonds of helix
Helix
Hydrogen bonds of sheet
Sheet
Residue 50~55
201~207
323~328
Number of helix ?
From residue 46~146
Change color
Visualization of biological assembly
-color by chain
Change color by chain
-act on Ribbons
Show residue properties
-Change color by Type
Type
Negative
Positive
Polar
Hydrophobic
Reisdue
ASP
GLU
HIS
LYS
ARG
SER
TYR
ASN
THR
GLN
CYS
MET
PHE
ALA
TRP
LEU
ILE
PRO
VAL
GLY
Show structure flexibility
Change color by B-factor
A low B-factor meaning that the position of the
atom has been determined with accuracy
High B-factor
Low B-factor
Other color types
default atom colors
Root mean square
between 2 molecules
Secondary Structure
Selected residues
Relative accessibility
Thymidine kinase
• Function: DNA synthesis
• Therapeutic: Anticancer and
antivirus drug target
Analyze protein-ligand interactions
-Select ligands (or residues)
Press left button of mouse
to select the ligand (THM, thymidine) of 1kim
Identify binding site
-Show protein (ribbon) and ligand (stick)
Select residues in the binding site
-Neighbors of selected residues
Center selected residues
H-bonds of the binding site
-Compute H-bonds
H-bonds between protein and ligand
-Show H-bonds of selection
H-bonds between TK and THM
-Show residues from selection
Show residue label
Press right button of mouse
1. Q125 recognize the thymine moiety
2. Activity was decreased by over
90% if Q125 mutated (Biochemistry, 2000.
39: p. 4105-4111)
van der Waal forces
-Stacking interactions
M128 and Y172 sandwich the thymine moiety Stabilize
the binding of substrate (JBC, 1999. 274: p. 31967-31973)
Observe the protein surface
-Compute Surface
Surface preference
Show ligand in the surface
Discard surface
Comparison of multiple structures
-Import PDB
PDB code: 3vtk
Another structure of thymidine kinase
Open layer info
Show or hide
1kim
3vtk
Superimpose two molecules
Results of superimposition
RMS: 0.63 Ǻ
Measure the structure similarity
Comparison of binding sites
-Neighbors of selected residues
Comparison of ligands
3vtk: inhibitor (Green)
1kim: substrate(CPK)
Save files
Homework
Keyword
1. Capture a picture of N1 neuraminidase (ribbon) and
its ligand (stick)
2. Capture a picture of H-bonds between protein and
ligand
E-mail
pikihsu@gmail.com
Mail title: 學號姓名_HW2