Proteins are Quantum Mechanical Machines

Leonor Cruzeiro

CCMAR and FCT,

University of Algarve

The F0 F1 ATP synthase

The VES hypothesis: the first step in protein function is the storing of energy in the form of quantum Vibrational Excited States.Conformational changes are driven by transient forces that arise from VES. [J.Phys.:Cond. Matter 17: 7833 (2005), JPOC 21: 549 (2008)].

VES: the drivers of conformational changes ?

A

Chemical Reactions Quantum Processes Quantum states(VES)

The question is thus not whether there are VES states in proteins, but:

1) What form they take2) How long they last,3) What role they have

Davydov/Scott model:

1) Amide I vibrations2) ps3) Energy transfer without dissipation

The Davydov/Scott Model

C

O

N

H

Generalized Davydov/Scott Model

N

mnnnnmeq

Nm

On

nph

N

mnnmmnnmn

N

nnqp

phqp

AAdRRH

RVH

AAAAJAAH

HHHH

1,int

1,1

int

ˆˆ)cos()|(|ˆ

})({

ˆˆˆˆˆˆˆ

ˆˆˆ

Equations of motion for amide I transport

nm

mnmn VE

nm

mnmn VE

First Application of the VES hypothesis: the structural instability of prions

Prions have large amounts of amino acids Gln and Asn.

Gln and Asn are the only two amino acids that can have amide I vibrations in their residues.

Without Gln and Asn, proteins can only exchange amide I vibrations through their backbones; but Gln and Asn can divert energy from the protein backbone to their residues.

The amide I mode is resonant with the bending mode of water.

Red < 0.3Yellow – [0.3,0.6]Green – 1Blue - > 1

PDB1QLXLeu 125-Arg 228

First Application of the VES hypothesis: the structural instability of prions

First Application of the VES hypothesis: the structural instability of prions

Average Vibrational Energy Transfer

to and from water

L. Cruzeiro, J. Phys.: Cond. Matter 17: 7833 (2005)

From water

To water

Second Application of the VES hypothesis: Huntington’s disease

L. Cruzeiro, J. Phys. Org. Chem 21: 549 (2008)

From water

To water

Average Vibrational Energy Transfer

to and from water from poly-glutamine-helix

Third Application of the VES hypothesis: Amide I band of an alpha-

helix

L. Cruzeiro, J. Chem. Phys. 123: 234909 (2005)

χ>0 χ<0

Thick line |χ|=62 pN, thin line |χ|=15 pN, very thin line χ=0

Proteins are Quantum Mechanical Machines

The first step in protein function is a quantum mechanical event, i.e it is the storing of energy in the form of vibrational excited states (VES hypothesis).

Prions and other proteins associated with misfolding diseases may be less stable because this exchange is enhanced by the presence of excess numbers of Gln and Asn.

Conformational changes arise when VES energy is converted into transient classical forces, i.e. proteins can convert a quantum event (VES) into a classical event (conformational changes).

The backbone of all proteins is a perfect medium to store and transfer energy in the form of VES.