Proteins and beyond
10
From Drug Design to Self-assembling Materials Ivan Coluzza
Transcript of Proteins and beyond
From Drug Design
to Self-assembling Materials
Ivan Coluzza
Proteins
A protein is made of a list of ~20 different types of amino acids
Proteins fold to thermodynamically stable structures at finite temperature called Native States
Design is the process of finding all sequences that can fold to a given configuration
http://xray.bmc.uu.se/~kurs/BiostrukfunkX2/practicals/practical_1/figs/peptide_bond.jpg
Folding vs DesignE =
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C̄ijSijE =
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EN =
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Folding Design
ADSVGCA......
Examples of caterpillar design - refolding
Lipoprotein (2K57)
C-Terminal domain of the Ribosomal Protein (1CTF)
Protein G (1PGB)Nuclear RNA export factor
(1OAI)Coluzza I., Plos ONE 10.1371/journal.pone.0020853 (2011)
Equatorial Region
Hydrophobic Trap
Hydrophilic Cage
~164
Å
GroEL/GroES Chaperonin
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Hydrophobic Hydrophilic Non-Native
Native State
2
3a
4b
4a
1
3b Trans refolding path Cis refolding path Shuttling
Chaperonin reaction pathway
Coluzza I., van der Vies S. M., Frenkel D. Biophysical Journal 90 (10): 3375-3381 (2006)
Artificial Protein
C 1 2
2.0 Ao
CC12
2.0 Ao
C
Hydrogen Bonds
Patchy-ParticlesHard Core Patch
Bond
Bianchi et al. Phys. Rev. Lett. (2006) vol. 97 (16) pp. 4
Patchy-Polymer structure space
a
b
c
1 Patch 2 Patches
Increasing interaction
range
Patchy polymersUnderstand protein folding and design
Structure Prediction Drug Design
Aggregation (Alzheimer) Chaperonin &
Folding under confinementProtein
Evolution
Macroscopic Folding
Direct conversion of simulations
results to experiments
Create a material design framework
AcknowledgementsChristoph Dellago
Cristos Likos
Barbara Capone
Peter van Oostrum
Ronald Zirbs
Erik Reimhult
Mark Miller
Michele Vendruscolo
Daan Frenkel
Angelo Cacciuto
Angel Orte
Maria Jose Ruedas
Saskia van der Vies
Francesco Sciortino
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Marie Curie Program for Intra-European Mobility Grants FP6
