Figure S1.

Hen Egg Lysozyme

Ln

PF

cal

Residue Number

1 21 41 61 81 101 121

Ln

PF

exp

H-COREX-CalculatedCOREX-CalculatedNMR-Determined

0

10

20

30

20

10

Figure S2.

Equine lysozyme

-18

-12

-6

0

6

12

18

Ln

PF

cal

Ln

PF

exp

1 21 41 61 81 101 121

Residue Number

18

12

6

0

6

18

12

H-COREX-CalculatedCOREX-CalculatedNMR-Determined

y = 0.91x - 0.23

R2 = 0.75

0

5

10

15

20

0 5 10 15 20Experimentally-determined

deuteron incorporation per peptide

DX

CO

RE

X-c

alc

ula

ted

d

eut

ero

n in

corp

ora

tion

pe

r pe

ptid

e

Figure S3.

Catalytic subunit of PKA E230Q

y = 1.06x + 0.15

R2 = 0.82

0

2

4

6

8

0 2 4 6 8Experimentally-determined

deuteron incorporation per peptide

DX

CO

RE

X-c

alc

ula

ted

d

eut

ero

n in

corp

ora

tion

pe

r pe

ptid

e

-actinin CH2 domain

Figure S4.

y = 0.73x + 0.45

R2 = 0.80

0

5

10

15

20

0 5 10 15 20Experimentally-determined

deuteron incorporation per peptide

DX

CO

RE

X-c

alc

ula

ted

d

eut

ero

n in

corp

ora

tion

pe

r pe

ptid

e

Rosiglitazone-bound PPAR LBD

Figure S5.

Figure S6.

y = 0.80x + 0.61R2 = 0.54

0

4

8

12

0 4 8 12

Experimentally-determined deuteron incorporation per peptide

DX

CO

RE

X-c

alcu

late

d de

uter

on in

corp

orat

ion

per

pept

ide(A)

y = 0.93x + 1.94R2 = 0.56

0

4

8

12

16

20

0 4 8 12 16 20

Experimentally-determined deuteron incorporation per peptide

DX

CO

RE

X-c

alcu

late

d de

uter

on in

corp

orat

ion

per

pept

ide(B)

pH = 6.1 pH = 8.8

Protein PDB ID Window size Number of microstates

Entropy factor (W)

PH T (0C)

Hen egg-white lysozyme 1HEL 8 50000 0.773 7.5 30

Equine lysozyme 2EQL 8 50000 1.02 4.5 25

Bovine pancreatic trypsin inhibitor 1BTI 6 126 0.65 3.5 30

Turkey ovomucoid third domain 2OVO 6 500 0.76 5 30

staphylococcal nuclease 1STN 12 2064 0.964 5.5 37

IB 1NFI 8 90000 1.097 7.5 25

D/D domain of type II isoform of PKA 1L6E 8 2000 0.85 6.9 23

Catalytic subunit of PKA E230Q 1SYK 8 70000 1 7.4 25

-actinin CH2 domain 2EYI 8 15000 0.75 7.0 4

hGHv 1HUW 8 40000 1 7.5 25

hGHv in the hGHv-hGHbp complex 1KF9 8 100000 1.05 7.5 25

Mitogen-activated protein kinase p38 1P38 8 80000 1.027 7.5 25

AlkB 2FD8 8 50000 1.026 7.0 4

Superoxide dismutase A4V 1UXM 8 40000 0.919 7.2 4

Superoxide dismutase WT 1PU0 8 40000 0.919 7.2 4

PPAR LBD 1PRG 8 110000 1.064 8.0 25

Rosiglitazone-bound PPAR LBD 2PRG 8 90000 1.085 8.0 25

Cerezyme 2NT1 8 110000 1.114 8.8 25

GVIA-2 iPLA2 catalytic domain N/A 8 70000 1.022 7 23

Study Proteins

Table S1.