Can we learn anything new from hydrogen bonds?
Marta Enciso Universidad Complutense de Madrid
BIFI 2011 - Marta Enciso
Wylie, JACS, 2009
Kannan, Int. J. Mol. Sci., 2009
Chen, PNAS, 2009
Dobson, Annu. Rev. Biochem., 2006
Proteins and hydrogen bonds
• Protein structure• Protein design• Folding• Aggregation
BIFI 2011 - Marta Enciso
• System description• Potential definition
– Geometrical restrictions– Energy calculation
• Simulation technique
ME & A. Rey, J. Chem. Phys., 2010
Our coarse grained approachDistance
Angle
BIFI 2011 - Marta Enciso
Frozen region
Meaningful region
ME & A. Rey, J. Chem. Phys., 2010
An homopeptide study
C
D B
A
BIFI 2011 - Marta Enciso
Protein studies I:Identification of hydrogen bonds
Domain B ofprotein A
-30
-20
-10
0
10
20
% e
xtra
hyd
roge
n bo
nds
dssp stride pymol ours
DSSPSTRIDEPyMOLOurs
fla
vodo
xin
dom
ain
B p
rote
in A
α-
spec
trin
T4 ly
sozy
me
fib
rone
ctin
PD
Z do
mai
n
BIFI 2011 - Marta Enciso
L. Prieto, D. de Sancho & A. Rey, J. Chem. Phys., 2005
Protein studies II:Protein folding and interprotein interactions
Protein Folding
Topology-based models
Protein Folding
Hydrophobics Hydrogenbonds +
BIFI 2011 - Marta Enciso
Protein studies II: folding
300 310 320 330 340 350 3600
5000
10000
15000
Topology-based model Topology-based model + hydrogen bond
Cv/
A. U
.
T /K20 40 60 80
20
40
60
80
# re
sidu
e
# residue*J. Clarke, JMB, 1997
Experiment* 4 K
Topology-based 8 K
Topology+HB 5 K
Peak width
Fibronectin type III domain
BIFI 2011 - Marta Enciso
Protein studies II: interprotein interactions
300 310 320 330 340 350 3600
5000
10000
15000
Cv/ A
. U.
T /K
Fibronectin type III domain
Two chains
Conclusions
BIFI 2011 - Marta Enciso
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
Acknowledgements
Grupo de Simulación de ProteínasDepartamento de Química Física IUniversidad Complutense de Madrid
Antonio ReyRamiro PerezzanDavid de Sancho (U. Cambridge)Lidia Prieto (CUNY)María Larriva (U. Navarra)
Can we learn anything new from hydrogen bonds?
Marta Enciso Universidad Complutense de Madrid
BIFI 2011 - Marta Enciso
Simulating hydrogen bonds
a) First principles – Quantum Mechanics
b) Empiric potentialsa) Atomic resolutionb) Coarse-grained models
a) Othersb) Our approach
• 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)
Model geometrical constrains
