close

Вход

Забыли?

вход по аккаунту

код для вставкиСкачать
Protein Folding, Bridging Lattice
Models and Reality
Skorobogatiy Maksim, Ned
Wingreen, Chao Tang
NEC, Princeton, NJ
The Protein Folding Problem
A Reductionist’s Approach
Real Problem
Simple Model
General Features
From Simple
Models
Physical Interactions
Van der Waals interaction
Electrostatic interaction
Hydrogen bonding
Hydrophobic interaction
A B
12  6
r
r
q1q2
r
Essentials for a “Minimal” Model
of Protein Folding
• Self-avoiding polymer
• At least two different types of monomers
• Short range contact interaction
HP Model on a Lattice
(Lau, Chan, Dill)
H   Es is j (ri  rj )
i j
Sequence {s}:
EHH  EHP  EPP
2D
Structure {r}:
3D
Designability of Structures
A structure S is designable by a sequence {s} if S is
the unique ground state of {s}
Number of structures
Designability Histogram
Number of sequences designing a structure
Most Designable Structures
a Helix
b Strand
Characterizing Highly
Designable Structures
What are the geometric properties which make
These structures special ?
0  corner


 Surface
1  edge 
2  Bulk

Nsb
Tsb 
 0.4
Nb
112222221101221122101122110122112210
Real Proteins
Implementation of Realistic
Geometries
Thermodynamics
F=E-TS=
NbbEbb+NwwEww+NwrEwr+NwbEwb-TSchain-TSsolution
Schain is simulated by MD or MC
Ssolution=NwwSww+NwrSwr+NwbSwb
Nww≈N0-Nwr-Nwb
F-N0(Eww-T Sww) ≈
NbbEbb+ Nwr((Ewr- Eww)-T(Swr-Sww))
+ Nwb((Ewb- Eww)-T(Swb-Sww))-TSchain
F-F0=
NbbEbb+ NwrEwr+ NwbEwb- TSchain
Compact Structures Space
F-F0=
-Nbb|Ebb|+ Nwr|Ewr|- Nwb|E|wb- TSchain
|Ebb|
|Ewb|
|Ewr|
Ebb < 0
Ewr > 0
Ewb < 0
Spanning the Phase-Space
Globular
a Helical
“Real” protein like
bStrand Globular
Coarse-Graining the Structures
110010111110000010100...
1  Bulk

0  Surface
Surface to Bulk Transition Rate
Nsb
Tsb 
Nb
Ns
Surface to Core Ratio Rsc 
Nb
Rate of Surface to Bulk
Transitions
1/--страниц
Пожаловаться на содержимое документа