Marta Enciso
Universidad Complutense de Madrid
•
•
•
•
Protein structure
Protein design
Folding
Aggregation
Wylie, JACS, 2009
Chen, PNAS, 2009
Kannan,
Int. J. Mol. Sci., 2009
Dobson, Annu. Rev. Biochem., 2006
BIFI 2011 - Marta Enciso
Distance
• System description
• Potential definition
– Geometrical restrictions
– Energy calculation
• Simulation technique
Angle
ME & A. Rey, J. Chem. Phys., 2010
BIFI 2011 - Marta Enciso
A
C
Meaningful
region
Frozen region
B
D
ME & A. Rey, J. Chem. Phys., 2010
BIFI 2011 - Marta Enciso
dssp
stride
pymol
ours
20
10
0
PyMOL
Ours
STRIDE
DSSP
-10
PDZ domain
fibronectin
T4 lysozyme
α-spectrin
-30
domain B protein A
-20
flavodoxin
% extra hydrogen bonds
Domain B of
protein A
BIFI 2011 - Marta Enciso
Protein Folding
Topology-based
models
Protein Folding
+
L. Prieto, D. de Sancho & A. Rey, J. Chem. Phys., 2005
BIFI 2011 - Marta Enciso
Fibronectin type III
domain
80
Topology-based model
Topology-based model + hydrogen bond
15000
Cv/ A. U.
# residue
60
10000
40
Peak width
5000
20
0
300
310
20
320
330
340
T /K
# residue
40
60
350
360
80
*J. Clarke, JMB, 1997
BIFI 2011 - Marta Enciso
Experiment*
4K
Topology-based
8K
Topology+HB
5K
Fibronectin type III domain
Two chains
Cv/ A. U.
15000
10000
5000
0
300
310
320
330
340
T /K
BIFI 2011 - Marta Enciso
350
360
A correct description of hydrogen bonds is necessary for
understanding protein folding and aggregation
We have designed a coarse-grained hydrogen bond
model
We have proved its validity for obtaining secondary
structure elements and detecting real hydrogen bonds
It can be successfully applied to the study of protein
folding and interprotein interactions
BIFI 2011 - Marta Enciso
Grupo de Simulación de Proteínas
Departamento de Química Física I
Universidad Complutense de Madrid
Antonio Rey
Ramiro Perezzan
David de Sancho (U. Cambridge)
Lidia Prieto (CUNY)
María Larriva (U. Navarra)
Marta Enciso
Universidad Complutense de Madrid
a) First principles – Quantum Mechanics
b) Empiric potentials
a) Atomic resolution
b) Coarse-grained models
a)
b)
Others
Our approach
BIFI 2011 - Marta Enciso
• R1 is a spatial restriction that designates the distance between the two
carbons of the hydrogen bonded residues
R1 = rij = rj − ri
• R2 is an orientational restrain which computes the cosine of the angle
associated to the relative orientation between the auxiliary vectors of both
residues
R2 = cos(hi, hj)
• R3 is also an orientational quantity that computes the cosine of the angle
between the direction of the tentative hydrogen bond in the model and each
of the auxiliary vectors; thus, R3 is independently calculated for both i and j
beads R3i and R3j
R3 = cos(hi, rij)
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Can we learn anything new from hydrogen bonds?