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 approachD

istanceAngle

BIFI 2011 - Marta Enciso

Frozen region

Meaningful region

ME & A. Rey, J. Chem. Phys., 2010

An homopeptide study

C

DB

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

rog

en

bo

nd

s

dssp stride pymol ours

DSSPSTRIDEPyMOLOurs

f

lavo

doxi

n

dom

ain

B p

rote

in A

α-s

pect

rin

T4

lyso

zym

e

fib

rone

ctin

P

DZ

dom

ain

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

# r

esi

du

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 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)

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 resolution

b) Coarse-grained modelsa) Others

b) 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