Protein%20Folding

1
Protein Structure and Dynamics
Zhijun Wu Department of Mathematics Program on
Bio-informatics and Computational Biology Iowa
State University Ames, Iowa
2
Protein Folding
LEU
ARG
ASN
PRO
ALA
ASN
GLN
GLU
GLU
VAL
GLU
GLU
ASN
VAL
LEU
ARG
PRO
ASN
ALA
GLN
. . .
3
Myoglobin, John Kendrew, 1962, Nobel Prize in
Chemistry
Photosynthetic Reaction Center, Johann
Deisenhofer, 1988, Nobel Prize in Chemistry
Prion, Stanley B. Prusiner, 1997, Nobel Prize in
Physiology and Medicine
4
Experimental Methods
NMR Spectroscopy
X-ray Crystallography
5
Holdings in the PDB Protein Data Bank
http//www.rcsb.org
6
Physical Properties
7
Mathematical Model
Initial-Value Problem
8
Numerical Solutions
x
x(t)
xk1
xk
t
tk
tk1
Verlet 1967
9
Time Scales for Protein Motion
Bond vibration
Isomeris- ation
Water dynamics
Helix forms
Fastest folders
Typical folders
Slow folders
10-15 femto
10-12 pico
10-9 nano
10-6 micro
10-3 milli
100 seconds
10
Folding of Villin Headpiece Subdomain (HP-36)
Duan and Kollman 1998
11
Alternative Approaches
Boundary-Value Formulation
Ron Elber 1996
12
Single Shooting
x1
x
x1 ?(v0) f(v0) ?(v0)-x1 f(v0) 0
x1
v0
x0
v0
t0
t1
t
Newtons Method
13
Multiple Shooting
x
fj(xj-1, vj-1, xj) ?j(xj-1, vj-1) - xj fj(
xj-1, vj-1, xj) 0 j 1, , m
?j
xm
(xj-1,vj-1)
x0
t0
tm
t
(Vedell and Wu 2005)
Newtons Method
14
Alternative Approaches
Energy Minimization
min E (x1, x2, , xn)
Scheraga, et al.
15
Energy Landscape
Peter Wolynes, et al.
16
Energy Transformation
Scheraga et al. 1989, Shalloway 1992, Straub 1996
17
Transformation Theory
High frequency components are reduced with
increasing ? values.
Wu 1996, More Wu 1997
18
Having puzzled the scientists for decades, the
protein folding problem remains a grand challenge
of modern science. The protein folding problem
may be studied through MD simulation under
certain boundary conditions. An efficient
optimization algorithm may be developed to obtain
a fast fold by exploiting the special structure
of protein energy landscape. The successful
simulation of protein folding requires correct
physics, efficient and accurate algorithms, and
sufficient computing power.