Results Database

Quantification of interactions between solutes and small model compounds

The preferential interaction (µ23) is dissected into contributions (α values) from each type of atom on the model compound, as described by the following equation:

math equationWhere µ23 quantifies the interaction between solute 2 (often a biopolymer or model compound) and solute 3 (often an osmolyte, denaturant, or Hofmeister salt), relative to their interactions with solvent water.  μ23 can be thought of as the free energy of transfer of the model compound (species 2) from water to a solution that is 1 molal in the solute (species 3).  Subscript i refers to each atom type on solute 2.  The α value quantifies the strength of the interaction potential of solute 3 with 1 Å2 of ASA (water-accessible surface area) of each atom type i on solute 2.  Software for measuring ASA can be found here.

The value of µ23 can also be interpreted in terms of the solute partitioning model (SPM) as in this equation:

SPM math equationWhere Kp is the ratio of local to bulk concentration of solute 3, b1ASA is the number of waters of hydration in two layers of water at the surface area of interest, and 55.5 is the molality of pure water.  

The same equation can be rewritten to solve for the α value in terms of the partition coefficient Kp:

 

 

 

 

 

 


Quantifying Interactions of Nucleobase Atoms with Model Compounds for the Peptide Backbone and Glutamine and Asparagine Side Chains in Water

[link to publication]

α-values (cal mol−1 molal−1 Å−2

nucleobase

surface type

ureamethylureaethylurea1,1-dimethylurea1,3-dimethylurea1,1-diethylurea
carbonyl sp2O−0.80 ± 0.05−0.23 ± 0.06−0.12 ± 0.060.06 ± 0.090.45 ± 0.050.71 ± 0.12

amino sp3N

−0.29 ± 0.04−0.46 ± 0.05−0.81 ± 0.05−1.23 ± 0.07−1.07 ± 0.05−1.64 ± 0.1
ring sp2N−0.70 ± 0.04−1.15 ± 0.08−1.36 ± 0.07−1.7 ± 0.1−1.13 ± 0.07−2.01 ± 0.13

methyl sp3C

−0.57 ± 0.03−0.80 ± 0.04 −1.01 ± 0.05−1.07 ± 0.06−1.33 ± 0.03−1.26 ± 0.08
ring sp2C−0.57 ± 0.02−1.3 ± 0.07 −1.57 ± 0.07−2.02 ± 0.07−1.92 ± 0.04−2.7 ± 0.1

 

µ23 values (cal mol-1 molal-1)

model compoundureamethylureaethylurea1,1-dimethylurea1,3-dimethylurea

1,1-diethylurea

naphthalene-166 ± 5.9-361 ± 15-390 ± 15-554 ± 33-568 ± 9.4-749 ± 14
anthracene-195 ± 5.9-475 ± 43-588 ± 40-697 ± 33-639 ± 24-914 ± 57
3-methylindole-156 ± 13-267 ± 12-367 ± 20-526 ± 27-436 ± 8.7---
caffeine-249 ± 11-308 ± 9.3-362 ± 17-375 ± 20-397 ± 7-462 ± 29
theophylline-211 ± 3.7-306 ± 10-379 ± 14-375 ± 30-387 ± 12-376 ± 18
theobromine-220 ± 14-290 ± 8.2-302 ± 14-398 ± 12-373 ± 15-460 ± 16
hypoxanthine-175 ± 8.1-224 ± 14-332 ± 11-397 ± 16-296 ± 12---
adenine-151 ± 3.9-317 ± 9.7-339 ± 7.8-437 ± 14-374 ± 9.1-597 ± 12
2,6-diamino purine-171 ± 6-282 ± 9.6-390 ± 7.9-542 ± 17-424 ± 9.4-667 ± 18
uric acid-236 ± 12-279 ± 14-283 ± 14-327 ± 16------
1,3-dimethyl-6-amino uracil-141 ± 6.5-213 ± 7.5-294 ± 7.1-324 ± 9.5-287 ± 7.9-341 ± 15
thymine-188 ± 2.4-196 ± 8.1-206 ± 13-273 ± 10.5-238 ± 3.7-290 ± 16
uracil-171 ± 16-163 ± 4.7-185 ± 7.9-190 ± 9.4-147 ± 3.1-267 ± 11
cytosine-143 ± 8-168 ± 6.7-193 ± 9.1-211 ± 4.9-200 ± 4.6-247 ± 15
5-amino uracil-151 ± 9.1-133 ± 7.1-184 ± 9.8-206 ± 6.6-156 ± 7.9-251 ± 24
6-amino uracil-159 ± 4.9-183 ± 7.5-249 ± 11-378 ± 21-257 ± 8.3-415 ± 19

 

Water accessible surface area (ASA) (Å2)

model compoundamide sp2 Oamide sp2 Naliphatic sp3 Camide sp2 C
urea47.9130.207.2
methylurea38.387.588.46.5
ethylurea38.382124.66.5
1,1-dimethylurea38.354.5148.76.2
1,3-dimethylurea28.744.9176.75.8
1,1-diethylurea35.750208.93.7

 


Experimental Atom-by-Atom Dissection of Amide-Amide and Amide-Hydrocarbon Interactions in H2O

[link to publication]

α-values (cal mol−1 molal−1 Å−2

 amide Oamide Naliphatic sp3Camide sp2Caromatic sp2C
urea-0.52 ± 0.04-0.09 ± 0.02-0.07 ± 0.01-0.69 ± 0.06-0.59 ± 0.01
methylurea0.52 ± 0.08-0.44 ± 0.03-0.31 ± 0.01-0.99 ± 0.07-1.36 ± 0.08
ethylurea0.79 ± 0.06-0.55 ± 0.02-0.43 ± 0.01-1.2 ± 0.05-1.61 ± 0.07
1,1-dimethylurea1.09 ± 0.07-0.61 ± 0.03-0.35 ± 0.01-1.53 ± 0.05-2.04 ± 0.08
1,3-dimethylurea1.68 ± 0.09-0.77 ± 0.03-0.56 ± 0.01-1.87 ± 0.06-1.95 ± 0.04
1,1-diethylurea1.73 ± 0.09-0.84 ± 0.03-0.64 ± 0.01-1.88 ± 0.07-2.7 ± 0.1
1,3-diethylurea2.35 ± 0.09-1.01 ± 0.04-0.76 ± 0.01-2.28 ± 0.07-2.97 ± 0.13
naphthalene-4.44 ± 0.80.85 ± 0.29-2.71 ± 0.07-2.88 ± 0.83---

 

Values of µ23 (or self-interaction  µ22ex/2) in (cal mol-1 molal-1)

 ureamethylureaethylurea1,1-dimethylurea1,3-dimethylurea1,1-diethylurea
urea(-42.4 ± 4.3)-37.8 ± 1.9-43.8 ± 2.3-35.7 ± 2.1-30.2 ± 1.1-39.7 ± 1.2
methylurea-37.8 ± 1.9(-38.6 ± 3.9)-59.4 ± 2.3-46.8 ± 2.1-59.1 ± 2.8-78.3 ± 1.9
ethylurea-43.8 ± 2.3-59.4 ± 2.3(-75.6 ± 7.6)-69.2 ± 2.7-83.1 ± 2.9-96.2 ± 2.7
1,1-dimethylurea-35.7 ± 2.1-46.8 ± 2.1-69.2 ± 2.7(-28.8 ± 2.9)-61.6 ± 1.9-77.7 ± 2.7
1,3-dimethylurea-30.2 ± 1.1-59.1 ± 2.8-83.1 ± 2.9-61.6 ± 1.9(-66.6 ± 6.7)-114 ± 3.6
1,1-diethylurea-39.7 ± 1.2-78.3 ± 1.9-96.2 ± 2.7-77.7 ± 2.7-114 ± 3.6(-115 ± 12)
1,3-diethylurea-40.3 ± 2.5-87.8 ± 3.3-102.7 ± 1.9-79.8 ± 2.8-125 ± 3.5-146 ± 4.5
 1,3-diethylureamalonamidepropionamidemethylacetamideAAMA
urea-40.3 ± 2.5-54.9 ± 2.5-36.8 ± 2-36.3 ± 1.7-52.4 ± 5.9
methylurea-87.8 ± 3.3-43.8 ± 1.4-62.3 ± 1.7-49.7 ± 1.8-61.3 ± 3.3
ethylurea-91.7 ± 2.7-48.5 ± 2.4-67.6 ± 1.7-72.2 ± 1.5-70.6 ± 1.7
1,1-dimethylurea-79.8 ± 2.8-30.6 ± 1.8-53.5 ± 2.3-42.2 ± 1.7-39.8 ± 2.3
1,3-dimethylurea-125 ± 3.5-27.3 ± 2.4-68.5 ± 1.9-66.2 ± 2.8-60.9 ± 2.6
1,1-diethylurea-146 ± 4.5-34.6 ± 1.3-78.2 ± 1.5-89 ± 1.9-78.3 ± 3.1
1,3-diethylurea(-133 ± 13)-21.7 ± 1.2-72.7 ± 2.5-87.1 ± 2.2-80.3 ± 2.9
 formamidemethylformamideanthracenenaphthalene
urea-62.9 ± 2.2-56.1 ± 2.9-194 ± 5.9-165 ± 5.9
methylurea-48.8 ± 3-53.7 ± 1.7-472 ± 43-359 ± 15
ethylurea-39.2 ± 1.1-74.9 ± 1.9-584 ± 40-387 ± 15
1,1-dimethylurea-51.6 ± 1.7-60.2 ± 1.7-693 ± 33-551 ± 32
1,3-dimethylurea-52.6 ± 1.6-66.7 ± 1.9-635 ± 24-565 ± 9.4
1,1-diethylurea-51.4 ± 1.7-77.5 ± 2.3-907 ± 56-691 ± 9.1
1,3-diethylurea-48.9 ± 1.3-81.6 ± 2.5-1064 ± 74-738 ± 16

 

Water accessible surface area (ASA) (Å2)

 amide sp2 Oamide sp2 Naliphatic sp3 Camide/aromatic sp2 C
urea

47.9

130.2

0

7.2
methylurea38.387.588.46.5
ethylurea38.382124.66.5
1,1-dimethylurea38.354.5148.76.2
1,3-dimethylurea28.744.9176.75.8
1,1-diethylurea35.750208.93.7
1,3-diethylurea28.733.8249.25.8
malonamide65.7123.248.58.5
propionamide36.861.6124.54.3
methylacetamide35.3191783.5
AAMA62.521.1257.74.3
formamide51.370.8040.2
methylformamide41.727.788.439.5
dimethylformamide41.70.8157.730.7
ethyleneurea4957.1113.67
dimethylacetamide35.30.8220.13.6
tetramethylurea29.90.8266.43.3
naphthalene000273
anthracene000338

 

Composite amide, hydrocarbon, and amide-hydrocarbon α-values to predict solute effects on protein folding

α-values (cal mol−1 molal−1 Å−2

 amidehydrocarboncombined
urea-0.39 ± 0.03-0.12 ± 0.01-0.18 ± 0.01
methylurea0.24 ± 0.06-0.42 ± 0.01-0.27 ± 0.02
ethylurea0.46 ± 0.12-0.55 ± 0.02-0.33 ± 0.03
butyl urea0.86 ± 0.04-0.82 ± 0.04-0.45 ± 0.03
1,1-dimethylurea0.59 ± 0.05-0.5 ± 0.01-0.26 ± 0.01
1,3-dimethylurea0.87 ± 0.08-0.67 ± 0.02-0.33 ± 0.02
1,1-diethylurea1.06 ± 0.10-0.87 ± 0.03-0.45 ± 0.03
1,3-diethylurea1.31 ± 0.18-0.96 ± 0.05-0.46 ± 0.05

 


Basis of protein stabilization by K Glutamate:  unfavorable interactions with carbon, oxygen groups.

[link to publication]

Values of µ23 for Interactions of KGlu with Model Compounds (cal mol-1 m-1)

Model Compoundexperimental µ23
acetyl-ala-methylamide406 ± 6
1,3-diethylurea348 ± 7
naphthalene322 ± 14
glycine betaine292 ± 4
benzene291 ± 11
1,1-diethylurea284 ± 4
1,3-dimethylurea249 ± 5
propionamide174 ± 6
proline161 ± 4
valine117 ± 5
methylurea111 ± 6
malonamide48 ± 2
alanine29 ± 2
urea31 ± 2
glycine-50 ± 4

 

KGlu-Group Interaction Potentials (α-values) and Corresponding Local-Bulk KGlu Partition Coefficients (Kp)

Surface Typeα (cal mol-1 m-1 Å2)SPM Kp
aliphatic sp3 C1.34 ± 0.020.63 ± 0.01
sp2 C1.25 ± 0.040.65 ± 0.01
amide O0.76 ± 0.150.79 ± 0.02
carboxylate O0.37 ± 0.070.9 ± 0.01
amide N -0.39 ± 0.071.11 ± 0.01
cationic N-1.87 ± 0.071.52 ± 0.01