Hydration of Small Peptides - UC Santa Barbara

85
Hydration of Small Peptides Thomas Wyttenbach, Dengfeng Liu, and Michael T. Bowers http://bowers.chem.ucsb.edu/

Transcript of Hydration of Small Peptides - UC Santa Barbara

Page 1: Hydration of Small Peptides - UC Santa Barbara

Hydration of Small Peptides

Thomas Wyttenbach, Dengfeng Liu,and Michael T. Bowers

http://bowers.chem.ucsb.edu/

Page 2: Hydration of Small Peptides - UC Santa Barbara

Why study hydration?Is a certain property of a molecule

(e.g. conformation)inherent to the molecule

or a consequence of solute–solvent interaction?

Page 3: Hydration of Small Peptides - UC Santa Barbara

water(theory)3

apolar solvent(NMR)1

water:2

• no NMR structure• no α-helix• no β-sheet• hydrophobic core

1 Crescenzi et al Eur J Biochem 269, 5642 (2002)

2 Zhang et alJ Struct Biology 130, 130 (2000)

3 Baumketner, SheaUCSB, unpublished

Alzheimer amyloid β-peptide

gasphase

(theory)3

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Why study hydration?

Bridge gas phase and solution phase

Study effect of individual water molecules on solute molecules

• energetics (water binding energy)

• structureconformations, foldingzwitterion formationhydration sites

Page 5: Hydration of Small Peptides - UC Santa Barbara

Myoglobin

NMR structure

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3

6

90

m/z

Mass SpectraNeurotensin

2 torr H2O286 K

(M+2H)2+

(M+3H)3+

(M+H)+

1 H2O(ELYENKPRRPYIL)

1

2

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ESI IonSource

ESI IonSource

IonFunnel

IonFunnel

DriftCell

DriftCell MSMS DetectorDetector

Instrumentation

M+ M+•(H2O)n

H2O

~1 torr H2O

Liquid N2 cooling

Electricalheaters

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3

6

90

m/z

Mass SpectraNeurotensin

2 torr H2O286 K

(M+2H)2+

(M+3H)3+

(M+H)+

1 H2O(ELYENKPRRPYIL)

1

2

M+ M+•(H2O)n

H2O

~1 torr H2Om/z

1800 µs

900 µs

2700 µs

drift time

Neurotensin (M+2H)2+

290 K, 1.8 torr H2O

Equilibrium?YES

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3

6

90

m/z

Mass SpectraNeurotensin

2 torr H2O286 K

(M+2H)2+

(M+3H)3+

(M+H)+

1 H2O(ELYENKPRRPYIL)

1

2

M+ M+•(H2O)n

H2O

~1 torr H2O

Equilibrium?

ratio ofpeak intensities

equilibriumconstant

van’t Hoff

∆H° and ∆S°

Data Analysis

∆H° ∆S°+

YES

⊕ ⊕

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• Amine

• Guanidine

• Imidazole

• Carboxylate

lysN-terminus

arg

his

aspgluC-terminus

In peptides and proteins they are:

Charged groups are important.

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Ionic Groups The Ammonium GroupThe Guanidinium GroupThe Carboxylate Group

Several Ionic GroupsMultiply Charged IonsSalt Bridges

Challenges AheadChange of ConformationZwitterion Formation

Entropy

HY

DR

AT

ION

OF

PE

PT

IDE

SH

YD

RA

TIO

N O

F P

EP

TID

ES

HY

DR

AT

ION

OF

PE

PT

IDE

S

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CH3NH3+

B3LYP/6-311++G**

2

13

4

secondsolvation

shell

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1 2 3 4 56

8

10

12

14

16

18 Experiment MM DFT

Number of water molecules

Wat

er b

indi

ng e

nerg

y (k

cal/m

ol)

n-decylamine

Experiment

second solvation shell

MolecularMechanicsAMBER, TIP3P

first solvation shell

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Ionic hydrogen bond:

δ+

δ–

electrostatic interaction important

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⊕⊕

δ+

δ+

17kcal/molexperiment1

& DFT2

15 kcal/molexperiment2

1 Meot-NerJACS 1984, 106, 1265

2 Liu, Wyttenbach, Barran, Bowers,JACS 2003, 125, 8458

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δ+

δ+

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M+•(H2O)n

103122151

∆H°kcal/mol

n

Page 19: Hydration of Small Peptides - UC Santa Barbara

0.100.903

0.080.922

0.050.951

—0.35 0.65

1.000

(H2O)nCH3—NH3+n

NBO charges onCH3NH3

+•(H2O)n

B3LYP/6-311++G**

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1 2 3 4 5

Experiment MM DFT

Number of water molecules

Exp Ele

Elec

tros

tatic

ene

rgy

Eel

n-decylamine

Electrostaticinteraction

∑∑=ij

jiel r

qqE

qi qjΣΣ=CH3NH3

+

(H2O)n–1

nth

H2O

n–1

qi

qj

etc.

etc.

n–1

qi

qj

etc.

etc.

2 kcal/mol

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1 2 3 4 5

Experiment MM DFT

Number of water molecules

Exp Ele

n-decylamine

Electrostaticinteraction

∑∑=ij

jiel r

qqE

qi qjΣΣ=CH3NH3

+

(H2O)n–1

nth

H2O

vsExperimental

water binding energy(C10H21NH3

+)

2 kcal/mol

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1 2 3 4 56

8

10

12

14

16

18 Experiment MM DFT

Number of water molecules

Wat

er b

indi

ng e

nerg

y (k

cal/m

ol) DFT

methylamine

Experimentn-decylamine

AMBERn-decylamine

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NH CH C

CH2

NH

O

CH2

CH2

CH2

NH3

C

O

CH C NH

O

R

Peptides

self-solvationH3C C NH2

O

δ+

δ–3.7 D

H3C C OH

O 1.7 D

δ+

δ–

lysine

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Nα-acetyl-L-lysineAMBER

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AMBER

δ+⊕

OH

Experimental binding energies(–∆H° in kcal/mol)

of nth water molecule

9.638.412.12

10.614.81

Nα-acetyl-L-lysine

n-decyl-amine

n

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NH CH C

CH3

NH

O

CH C

CH3

NH

O

CH C

CH2

NH

O

CH2

CH2

CH2

NH2

CH C

CH3

NH

O

CH C

CH3

OH

O

CH3C

O

Ac-AAKAA

AMBER

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NH CH C

CH3

NH

O

CH C

CH3

NH

O

CH3C

O

CH C

CH3

NH

O

CH C

CH3

NH

O

CH C

CH2

OH

O

CH2

CH2

CH2

NH2

Ac-AAAAK

chargeremote

AMBER

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Ac-AAKAA vs Ac-AAAAK

AMBER

8.5kcal/mol

experimentalwater binding

enthalpy6.9

kcal/mol

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Ac-AxK

(c)

NH3+NH3+⊕δ–

δ+

α-helix

AMBER AMBERx = 8x = 20 Jarrold JACS (1998) 120, 12974

x = 4

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Experimental water binding energies (kcal/mol)

n/an/an/a

7

8

Ac-A20K

Ac-A8K

Ac-AAAAK

Ac-AAKAA

n-decylamine 101215

≤4n/an/an/a5n/an/an/a7n/an/an/a79n/an/a

n/a

321

First solvation shell Secondsolvation

shellChargeremote

10 8 8acetyllysine

a

a Estimated based on: Jarrold JACS (2002) 124, 11148

Ammonium Group

Page 31: Hydration of Small Peptides - UC Santa Barbara

Ionic Groups The Ammonium GroupThe Guanidinium GroupThe Carboxylate Group

Several Ionic GroupsMultiply Charged IonsSalt Bridges

Challenges AheadChange of ConformationZwitterion Formation

Entropy

HY

DR

AT

ION

OF

PE

PT

IDE

SH

YD

RA

TIO

N O

F P

EP

TID

ES

HY

DR

AT

ION

OF

PE

PT

IDE

S

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HO

HN

NH3

O

O

CH3

CH3

NH2

NH2

NHHO

O

NH2

(Arg–OMe + H)+ 9.2C10H21NH3+ 14.8

(Arg + H)+ 9.0(Ala-Ala + H)+ 14.8–∆H° (kcal/mol)–∆H° (kcal/mol)

GuanidineAmine

Experimental water binding energies

Page 33: Hydration of Small Peptides - UC Santa Barbara

N

CN N

H

H

H

H

H

R = arginine

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Ac-AAAAK vs Ac-AAAAR

ArgLys

⊕⊕

AMBER

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9.49.5

10.29.3

9.0

–∆H°kcal/mol

(Ac-AAAAK + H)+

(Ac-AAKAA + H)+

(AAAAA + H)+

C10H21NH3+

(AARAA-OMe + H)+

(Ac-AARAA + H)+6.9(AARAA + H)+8.5(RAAAA + H)+10.5

(Arg + H)+Exposed14.8

–∆H°kcal/mol

Self-solvated

Amines Guanidinespe

ntap

eptid

esExperimental water binding energies

Page 36: Hydration of Small Peptides - UC Santa Barbara

Guanidines –∆H° kcal/mol

9.49.5

10.29.3

1st H2O

8.48.18.47.8

2nd H2O

7.6

7.1

3rd H2O

(AARAA-OMe + H)+

(Ac-AARAA + H)+

(AARAA + H)+

(RAAAA + H)+

Experimental water binding energies

Page 37: Hydration of Small Peptides - UC Santa Barbara

Ionic Groups The Ammonium GroupThe Guanidinium GroupThe Carboxylate Group

Several Ionic GroupsMultiply Charged IonsSalt Bridges

Challenges AheadChange of ConformationZwitterion Formation

Entropy

HY

DR

AT

ION

OF

PE

PT

IDE

SH

YD

RA

TIO

N O

F P

EP

TID

ES

HY

DR

AT

ION

OF

PE

PT

IDE

S

Page 38: Hydration of Small Peptides - UC Santa Barbara

Carboxylate(Ala-Ala – H)–

Ammonium(Ala-Ala + H)+

H2N CH C

CH3

NH

O

CH COO

CH3

H3N CH C

CH3

NH

O

CH COOH

CH3

Ala-Ala

14.8

–∆H°kcal/mol

1st H2O 11.61st H2O

–∆H°kcal/mol

8.53rd H2O8.93rd H2O

9.42nd H2O10.52nd H2O

Page 39: Hydration of Small Peptides - UC Santa Barbara

1

24

N CH C

CH3 O

OH

+ 4 H2O

3AMBER

firstsolvationshell

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(Ala-Ala – H)–

AMBER11.9

13.1

15.6

B3LYP/6-31G*

Calculated (B3LYP/6-31G*)water binding energy (kcal/mol)

Page 41: Hydration of Small Peptides - UC Santa Barbara

CH C

CH3

N

O

CH C

(CH2)x

N

O

CO O

CH C

CH3

O

H H

Peptide self-solvation

x=1 aspartic acidx=2 glutamic acid

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(Ala-Ala) • (Ala-Ala – H)–

AMBER

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4

3

[(AA)2-H]-

0 2 4 6 8

(AA–H)–•(AA)•(H2O)m

Dimer

(AA–H)–•(H2O)n

Monomer

n

319

8

3

160 180 200 220 240 260 280 300

320 340 360 380 400 420 440 460 480

m/z

1.3 Torr H2O, 260 K

⟨n⟩ – ⟨m⟩ ≅ 4

(AA–H)–•(H2O)5.2

Average: ⟨n⟩ = 5.2

(AA–H)–•(AA)•(H2O)1.3

Average: ⟨m⟩ = 1.3

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AMBER

(AA–H)–

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AMBER

(AA–H)–•(AA)

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AMBER

(AA–H)–•(H2O)4

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AMBER

Overlap of (AA–H)–

conformation in(AA–H)–

(AA–H)–•(H2O)4(AA–H)–•(AA)

Page 49: Hydration of Small Peptides - UC Santa Barbara

Ionic Groups The Ammonium GroupThe Guanidinium GroupThe Carboxylate Group

Several Ionic GroupsMultiply Charged IonsSalt Bridges

Challenges AheadChange of ConformationZwitterion Formation

Entropy

HY

DR

AT

ION

OF

PE

PT

IDE

SH

YD

RA

TIO

N O

F P

EP

TID

ES

HY

DR

AT

ION

OF

PE

PT

IDE

S

Page 50: Hydration of Small Peptides - UC Santa Barbara

Experimental binding energiesof nth water molecule

13.64

13.4312.12

15.72

15.7114.81

–∆H°kcal/mol

n–∆H°kcal/mol

n

H3N H3N

NH3

CH3(CH2)9NH3+ H3N(CH2)12NH3

2+Blades, Klassen, KebarleJACS 118, 12437 (1996)

Na+ Ca2+n1 ~5524

(radius 0.97 Å) (radius 0.99 Å)

Na+ Ca2+n1 ~5524

(radius 0.97 Å) (radius 0.99 Å)

Page 51: Hydration of Small Peptides - UC Santa Barbara

m/z

Hydration Mass SpectraNeurotensin

1.3 Torr H2O260 K

(ELYENKPRRPYIL)

96

3

820 840 860 880 900 920 940 960

12

12

H2O

560 580 600 620 640 660 680 700

15

189

1660 1700 1740 1780 1820

3

(M+2H)2+

(M+3H)3+

(M+H)+6

0

0

0

Page 52: Hydration of Small Peptides - UC Santa Barbara
Page 53: Hydration of Small Peptides - UC Santa Barbara

n −∆H°n (kcal/mol)

+1 +2 +3 1 9.2 10.3 (15) 2 9.8 8.9 (12) 3 (9) 9.6 9.5 4 (9) 9.4 9.3 5 8.5 9.4 6 (8) 9.8 7 (9) 8.8 8 (10) 9 (9) 10 (9)

Experimental ∆H°-values for binding nth water molecule to neurotensin (ELYENKPRRPYIL) in charge states +1, +2, and +3

± 0.3 kcal/mol± 1 kcal/mol for values in parenthesis

910 1210

10

10

9

8

9

Page 54: Hydration of Small Peptides - UC Santa Barbara

n −∆H°n (kcal/mol)

+1 +2 +3 1 9.2 10.3 (15) 2 9.8 8.9 (12) 3 (9) 9.6 9.5 4 (9) 9.4 9.3 5 8.5 9.4 6 (8) 9.8 7 (9) 8.8 8 (10) 9 (9) 10 (9)

Experimental ∆H°-values for binding nth water molecule to neurotensin (ELYENKPRRPYIL) in charge states +1, +2, and +3

± 0.3 kcal/mol± 1 kcal/mol for values in parenthesis

13.64

13.4312.12

15.72

15.7114.81

–∆H°kcal/mol

n–∆H°kcal/mol

n

13.64

13.4312.12

15.72

15.7114.81

–∆H°kcal/mol

n–∆H°kcal/mol

n

CH3(CH2)9NH3+ H3N(CH2)12NH3

2+Blades, Klassen, KebarleJACS 118, 12437 (1996)

H3N

NH3

H3N

NH3Degree of charge exposureNature of charged groups

Page 55: Hydration of Small Peptides - UC Santa Barbara

n −∆H°n (kcal/mol)

+1 +2 +3 1 9.2 10.3 (15) 2 9.8 8.9 (12) 3 (9) 9.6 9.5 4 (9) 9.4 9.3 5 8.5 9.4 6 (8) 9.8 7 (9) 8.8 8 (10) 9 (9) 10 (9)

Experimental ∆H°-values for binding nth water molecule to neurotensin (ELYENKPRRPYIL) in charge states +1, +2, and +3

± 0.3 kcal/mol± 1 kcal/mol for values in parenthesis

⊕⊕

⊕⊕

Degree of charge exposureNature of charged groups

Page 56: Hydration of Small Peptides - UC Santa Barbara

n −∆H°n (kcal/mol)

+1 +2 +3 1 9.2 10.3 (15) 2 9.8 8.9 (12) 3 (9) 9.6 9.5 4 (9) 9.4 9.3 5 8.5 9.4 6 (8) 9.8 7 (9) 8.8 8 (10) 9 (9) 10 (9)

± 0.3 kcal/mol± 1 kcal/mol for values in parenthesis

Experimental ∆H°-values for binding nth water molecule to neurotensin (ELYENKPRRPYIL) in charge states +1, +2, and +3Experimental ∆H°-values for binding nth water molecule to neurotensin (ELYENKPRRPYIL) in charge states +1, +2, and +3

+1 +2

Experimental ∆H°-values for binding nth water molecule to neurotensin (ELYENK

+3

Degree of charge exposureNature of charged groups

⊕⊕

⊕⊕

Expect 15 kcal/mol for exposed ammonium

independent of the presence of other charges

Page 57: Hydration of Small Peptides - UC Santa Barbara

(A) number of preferred hydration sites ∝ z(B) water binding energy ≠ f(z)

Multiply Charged Ions

(A) H3N

NH3

(B)

Page 58: Hydration of Small Peptides - UC Santa Barbara

Ionic Groups The Ammonium GroupThe Guanidinium GroupThe Carboxylate Group

Several Ionic GroupsMultiply Charged IonsSalt Bridges

Challenges AheadChange of ConformationZwitterion Formation

Entropy

HY

DR

AT

ION

OF

PE

PT

IDE

SH

YD

RA

TIO

N O

F P

EP

TID

ES

HY

DR

AT

ION

OF

PE

PT

IDE

S

Page 59: Hydration of Small Peptides - UC Santa Barbara

Same sign vs opposite sign charges

Coulomb repulsion Coulomb attraction⊕

Page 60: Hydration of Small Peptides - UC Santa Barbara

Salt Bridge

Salt Bridge

N

CN N

H

H

H

H

H

O OC

N

CN N

H

H

H

H

H

O OC

N

CN N

H

H

H

H

H

O

O

C

N

CN N

H

H

H

H

H

O

O

C

N

H

H

O

O

C

H

N

H

H

O

O

C

H

Page 61: Hydration of Small Peptides - UC Santa Barbara
Page 62: Hydration of Small Peptides - UC Santa Barbara

⊕δ+δ–

δ+δ–

Bradykinin

AMBER Barran, Liu, Wyttenbach, Bowers; unpublished

Page 63: Hydration of Small Peptides - UC Santa Barbara

⊕δ+δ–

δ+δ–

⊕δ+δ–

δ+δ–

AMBER

Page 64: Hydration of Small Peptides - UC Santa Barbara

Experimental ∆H° and ∆S° values for bindingnth water molecule to bradykinin (M+H)+

2710.24

2610.13

2510.12

2610.71

–∆S°kcal/mol

–∆H°kcal/moln

±0.3 ±1

Bradykinin

Page 65: Hydration of Small Peptides - UC Santa Barbara

Understand first steps of hydration:• Water binding sites• Energetics

for given peptide/protein structure.

However, peptide/protein structurechanges as hydration proceeds.

• Conformation• Zwitterion formation

Hydration Sites & Energies

Page 66: Hydration of Small Peptides - UC Santa Barbara

Ionic Groups The Ammonium GroupThe Guanidinium GroupThe Carboxylate Group

Several Ionic GroupsMultiply Charged IonsSalt Bridges

Challenges AheadChange of ConformationZwitterion Formation

Entropy

HY

DR

AT

ION

OF

PE

PT

IDE

SH

YD

RA

TIO

N O

F P

EP

TID

ES

HY

DR

AT

ION

OF

PE

PT

IDE

S

Page 67: Hydration of Small Peptides - UC Santa Barbara

Change of Conformation

H2O

aqAlzheimer amyloid β-peptide

Page 68: Hydration of Small Peptides - UC Santa Barbara
Page 69: Hydration of Small Peptides - UC Santa Barbara

ESI IonSource

ESI IonSource MSMS Drift Cell

(helium)Drift Cell(helium) MSMS DetectorDetector

form M±z•(H2O)n in the source

Measure collision cross sections of hydrated ions in helium

Williams, J. Am. Soc. Mass Spectrom. 1997, 8, 565Beauchamp, J. Am. Chem. Soc. 1998, 120, 11758.

measure cross sections in heliumWyttenbach, Bowers, Top. Curr. Chem. 2003, 225, 207.

Page 70: Hydration of Small Peptides - UC Santa Barbara

Ionic Groups The Ammonium GroupThe Guanidinium GroupThe Carboxylate Group

Several Ionic GroupsMultiply Charged IonsSalt Bridges

Challenges AheadChange of ConformationZwitterion Formation

Entropy

HY

DR

AT

ION

OF

PE

PT

IDE

SH

YD

RA

TIO

N O

F P

EP

TID

ES

HY

DR

AT

ION

OF

PE

PT

IDE

S

Page 71: Hydration of Small Peptides - UC Santa Barbara

H2O

aq

H3N CH2 C

O

O

H2N CH2 C

OH

O

Glycine

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neutral

Gly zwitter-ion

TheoryJensen and Gordon JACS, 117, 8159 (1995)Gly•(H2O)2

12 kcal/mol

zwitter-ion

Photoelectron spectroscopyXu, Nilles, BowenJ.Chem.Phys., 119, 10696 (2003)

zwitter-ion

Gly•(H2O)5

Glycine

kcal/moldrop per H2O

Page 73: Hydration of Small Peptides - UC Santa Barbara

2NNH

NH NHO

O

O

O

O

OH

D vs Lresidue

NHNH

NHNH

O

O

O

O

NH

H2N NH2+

H3N+

O

O–

Peptides

H3N CH2 C

O

O

HO

NH

H2N NH2+

HO

NH

H2N NH2+

AARAA

Page 74: Hydration of Small Peptides - UC Santa Barbara

AARAAdifferent

2NO

RNHOR’

2NNH

NH NHO

O

O O

residue

NHNH

NHNH

O

O

O

O

NH

H2N NH2+

O

500 502 504

MH

458 460 462 464 466 468 4700

25

50

75

100

AARAA

MH

m/z72 474 476 4

AARAR = AcR’= H

gas-phaseH/D exchange

with D2O

R = HR’= H

R = H R’= CH3

zwitterion

+all1Hall1H

Wyttenbach, Paizs, Barran, Breci, Liu, Suhai, Wysocki, Bowers

JACS 125, 13768 (2003)

Page 75: Hydration of Small Peptides - UC Santa Barbara
Page 76: Hydration of Small Peptides - UC Santa Barbara

AARAAdifferent

+1.80.0

(AARAA)H+·H2O

+4.80.0

(AARAA)H+

Energy (kcal/mol)AMBER & B3LYP/6-31+G(d,p)

zwitterion

neutral termini

different

2NO

H2NOH

2NNH

NH NHO

O

O O

residue

NHNH

NHNH

O

O

O

O

NH

H2N NH2+

O

Wyttenbach, Paizs, Barran, Breci, Liu, Suhai, Wysocki, Bowers

JACS 125, 13768 (2003)kcal/mol

drop per H2OCAUTIONwith interpretation of

gas-phase H/D exchange

data

Page 77: Hydration of Small Peptides - UC Santa Barbara

binding energy (kcal/mol)

AARAA

10.2 ± 0.3Experiment

8.9Theory

B3LYP/6-31+G(d,p)BSSE & ZPE correction

(AARAA)H+···H2O

Wyttenbach, Paizs, Barran, Breci, Liu, Suhai, Wysocki, Bowers

JACS 125, 13768 (2003)

Page 78: Hydration of Small Peptides - UC Santa Barbara

C-terminus

N-terminus

Wyttenbach, Paizs, Barran, Breci, Liu, Suhai, Wysocki, Bowers

JACS 125, 13768 (2003)

B3LYP/6-31+G(d,p)

set up forH/D exchange

relay mechanism

(AARAA)H+•H2ONeutral termini

Page 79: Hydration of Small Peptides - UC Santa Barbara

(AARAA)H+•H2OZwitterion

C-terminus

N-terminus

Wyttenbach, Paizs, Barran, Breci, Liu, Suhai, Wysocki, Bowers

JACS 125, 13768 (2003)

B3LYP/6-31+G(d,p)

Page 80: Hydration of Small Peptides - UC Santa Barbara

(AARAA)H+•H2OTransition state

C-terminus

N-terminus

Wyttenbach, Paizs, Barran, Breci, Liu, Suhai, Wysocki, Bowers

JACS 125, 13768 (2003)

B3LYP/6-31+G(d,p)

Page 81: Hydration of Small Peptides - UC Santa Barbara

Ionic Groups The Ammonium GroupThe Guanidinium GroupThe Carboxylate Group

Several Ionic GroupsMultiply Charged IonsSalt Bridges

Challenges AheadChange of ConformationZwitterion Formation

Entropy

HY

DR

AT

ION

OF

PE

PT

IDE

SH

YD

RA

TIO

N O

F P

EP

TID

ES

HY

DR

AT

ION

OF

PE

PT

IDE

S

Page 82: Hydration of Small Peptides - UC Santa Barbara

–∆S°cal/mol/K

–∆H° kcal/mol

all other data:• all molecules• all charge states• all hydrates 1st–nth H2O

1st H2Oon small

molecules

2nd H2Oon small

molecules

1st H2Oon small

molecules

∆S° < 0loss of 3 translational

and 3 rotational degrees of freedom(gain of 6 vibrationaldegrees of freedom)

all datapositive andnegative ions

floppy

Page 83: Hydration of Small Peptides - UC Santa Barbara

tightly bound H2O• large binding energy• large loss of entropy

strong entropy–enthalpy correlation (red data)

exceptions are:

• Addition of 1st H2O to small molecules (blue data) yields smaller than average loss of entropy→ floppy hydrates

• Addition of 2nd H2O to small molecules (yellow data) yields data between blue and red

Page 84: Hydration of Small Peptides - UC Santa Barbara

Understand first steps of hydration:• Water binding sites• Water binding energies• Loss of entropy

Future challenges include:• Hydration beyond the first steps• Change of protein conformation• Zwitterion formationH

YD

RA

TIO

N O

F P

EP

TID

ES

HY

DR

AT

ION

OF

PE

PT

IDE

SH

YD

RA

TIO

N O

F P

EP

TID

ES

?

Page 85: Hydration of Small Peptides - UC Santa Barbara