1. From
Drug Design
to
Self-assembling Materials
Ivan Coluzza

2. 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

3. Folding vs Design
E= Cij Sij
ij
Folding Design
E= ¯
Cij Sij E= ¯
Cij Sij
ij ij
ADSVGCA......
EN = ¯ ¯
Cij Sij
ij

4. Examples of caterpillar
design - refolding
Nuclear RNA C-Terminal domain
export factor
Lipoprotein of the Ribosomal Protein G (1PGB)
(1OAI) (2K57) Protein (1CTF)
Coluzza I., Plos ONE 10.1371/journal.pone.0020853 (2011)

5. GroEL/GroES Chaperonin
Hydrophilic
Cage
Equatorial Region
~164 Å
Hydrophobic
Trap

6. Chaperonin reaction pathway
Hydrophobic
Hydrophilic
4a Non-Native
Native State
2
1 4b
Trans refolding path 3b
Cis refolding path 3a
Shuttling
! !
Coluzza I., van der Vies S. M., Frenkel D. Biophysical Journal 90 (10): 3375-3381 (2006)

7. Artificial Protein
Hydrogen Bonds
C
Patchy-Particles
1 2
C
o
2.0 A
2.0 A
o
Hard Core Patch
C
2 1 C
Bond
Bianchi et al. Phys. Rev. Lett. (2006) vol. 97 (16) pp. 4

8. Patchy-Polymer structure space
1 Patch 2 Patches
a
Increasing
interaction
b range
c

9. Understand protein
Patchy polymers
folding and design
Structure Macroscopic
Drug Design
Prediction Folding
Aggregation
(Alzheimer) Chaperonin & Direct conversion
Folding under of simulations
confinement results to
Protein
experiments
Evolution
Create a material
design framework

10. ! 86"9/2)0:%')-,(6$
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Acknowledgements
12/$"(-"%0>"6%2,6$%
!
! ?6"9('(0@($)2A-"%'%
Christoph Dellago
! :6%2*6%01/B26$
Cristos Likos
Barbara Capone Marie Curie Progra
Peter van Oostrum
!
Grants FP6 !
Ronald Zirbs
Erik Reimhult
Mark Miller
Michele Vendruscolo
Daan Frenkel
Angelo Cacciuto
Angel Orte
Maria Jose Ruedas
Saskia van der Vies
Francesco Sciortino