Water

Buried Water Molecules-Binding-Reactions

Surface Water Molecules-Structure-Dynamics-Effect on Protein Motions

Water in and on Proteins

A-insideB-low densityC-high densityD-bulk

MD Simulation of Myoglobin

Svergun et al:

First 3Å hydration layer around lysozyme ~10% denser than bulk water

Lysozyme in explicit water

Low q :Size

Radius of Gyration (Rg)

Include Higher q :Chain Configurational

Statistics

q(Å-1)

P(q)

Small Angle Neutron Scattering

rijbibj

0 0.1 0.2 0.30

0.2

0.4

0.6

0.8

1

ki

kf

ki

kfq

array detector

Sample

L ~ 5 - 50 m

n

1i

n

1jji qrij

qrsin ijbb

n21

)q(PqR

3

11~)q(P 2

g

0q

First 3Å hydration layer around lysozyme ~10% denser than bulk water

Surface Water Molecules-Structure

Svergun et al PNAS 95 2667 (1998)

Geometric Rg from MD simulation = 14.10.1Å

SMALL-ANGLESCATTERING

RADII OF GYRATION

o(d)- (d) = Perturbation from Bulk

o(d) 10% increase

5% increase

Radial WaterRadial WaterDensity ProfilesDensity ProfilesProtein

Water (d)

(d)

Bulk Water Average Density

Bulk Water

d

Bulk Water

o(d) Present Even if Water UNPERTURBED from Bulk

What determines variationsin surface water density?

Simple View of Protein SurfaceSimple View of Protein Surface

(1) Topography

Protuberance

Depression

(2) Electric Field

qi

qj

qk

h=Surface Topographical Perturbation

L=17surface

L=3surface

Surface Topography, Electric Field and Density VariationsSurface Topography, Electric Field and Density Variations

Low

High

O

H HHigh

High

Water Dipoles Align withProtein E Field

Water Density Variations Correlated with Surface Topography and Local E Field from Protein

Physical Picture:Physical Picture:

Hydration of hydrophobic molecules

Small molecules• Bulk-like water • “WET”

Large Exposed Surface Area

• Fewer hydrogen bonds

•“DEWETTING”

Same effect in peptides?

Prion Peptide - MKHMAGAAAAGAVV

Exposed Hydrophobic Surface Area (nm2)

Hyd

rati

on S

hell

Den

sity

(nm

-2)

densityaround hydrophilicgroups

density around hydrophobicgroups

“DRY”

“WET”

hydrophobic analog

ISABELLADAIDONESame effect in peptides?

LowestFreeEnergy

Free Energy Profile

Met 109 (H) –Val 121 (O) (nm)

0 0.2 0.4 0.6 0.8 1.0 1.2 1.4

Stable at Low Hydration Density

Stable at High Hydration Density

Hydrophobic Hydration Shell Density (nm-2)

1. MD Simulations and Normal Mode Analysis of Myoglobin

2. Langevin Analysis of each ´´MD normal mode´´ Velocity Correlation Function

(0) ( ) exp( / 2)(cos sin )2nn

nn nn n nn

v v t t t t

KEIMORITSUGUEffect of Water on Protein Vibrations

Effect of Hydration on Protein Vibrational Motions

solvation

vacuum PES water PES

Increase of friction Shift to high frequencies

Friction changes Frequency shifts

Protein:Protein Interactions.Vibrations at 150K

VANDANAKURKAL-SIEBERT

1. MD Simulation

2. Langevin Analysis of Principal Component Coordinate Autocorrelation Function.

0

0

exp( / 2)(cos( s 10) ( ) ( )1

in ))

2

exp(vv v v

vn n t t tx

t

tx t

KEIMORITSUGUDiffusive and Vibrational Components

Diffusion-Vibration Langevin

Description of Protein Dynamics

Linear increase of vibrational fluctuationsv.s.

Dynamical transition of diffusive fluctuations

KEIMORITSUGU

Assume Height of Barrier given by Vibrational Amplitude.

Find: V~