Supporting Information
Lone pair ∙∙∙ π interactions between water oxygens and
aromatic residues: Quantum chemical studies based on
high-resolution protein structures and model compounds.
Alok Jain1, Venkatnarayan Ramanathan2 and Ramasubbu Sankararamakrishnan1*
1
Department of Biological Sciences and Bioengineering and 2Department of Chemistry
Indian Institute of Technology Kanpur, Kanpur-208016 (UP), India
Corresponding author E-mail: rsankar@iitk.ac.in. Telephone: (+91)-512-2594014
Fax: (+91)-512-2594010
S1
Figure S1
Figure S1: Influence of water hydrogen atoms even when they are maximally displaced
away from the aromatic center. Two orientations of water molecules are shown. In (A),
the minimum distance between water hydrogens and indole nitrogen atom is 3.83 Å and
in (B), it is 4.00 Å. Apart from this difference, all parameters such as d and δ are same for
both the structures. The interaction energy is more favorable for (B) (-1.27 kcal/mol)
compared to (A) (-0.78 kcal/mol). Such a small displacement (0.17 Å) of water hydrogen
atoms has resulted in interaction that is ~ 0.5 kcal/mol more favorable.
S2
Figure S2
Figure S2: Plot of a regression between the minimum distance of water hydrogen atoms
from the indole nitrogen and the interaction energy calculated between a water molecule
and the 5-membered indole ring. The water orientations were generated by rotating the
water molecule about the five-fold rotational axis of the pyrrole ring of the indole moiety
by fixing d at 3.2 Å.
S3
Figure S3
Figure S3: Water – Histidine interaction in the protein methionine aminopeptidase (PDB
ID: 1C24; chain id: A) involving His236 and HOH7. Hydrogen atom coordinates were
generated using GROMACS-OPLS (top) and InsightII (bottom). Residues within 3.5 Å
of imidazole nitrogen atoms and that form hydrogen bonds are displayed. In top, His236
is protonated and participates in hydrogen bond interactions with Asp254 and Thr249 and
in both cases, it donates proton to the side-chain oxygens. In bottom, His236 is neutral.
As observed in the previous case, it is involved in hydrogen bond interactions with both
Asp254 and Thr249. In the former case, it behaves as donor and in the latter case, the Nδ
atom of His plays the role of acceptor atom. Distance between the water oxygen and
aromatic center is displayed. Protonation state of histidine residue heavily influences the
strength of lone –pair …π electron interaction between the water oxygen and the aromatic
center. All the distances between hydrogen and heavy atoms of hydrogen bond
interactions are also shown. Residues are shown in one letter code with their residue
numbers. The following color coding is used for atoms – oxygen: red; nitrogen: blue;
carbon: grey; hydrogen: white
S4
Table S1: Optimal binding energies of water-aromatic systems at δ = 0º and δ = 90ºa
Aromatic
Distance d (Å)b
MP2/6-311++G (d,p) binding
energy in kcal/mol
Benzene
3.30
3.40
3.30
3.20
3.20
3.20
3.20
3.30
3.30
3.30
3.20
2.90
-1.44
-0.17
-1.47
-0.54
-1.66
-0.83
-1.69
-0.26
-1.70
-0.47
-4.02
-9.25
Imidazole
Indole_5
Indole_6
Phenol
Protonated
imidazole
aData in top and bottom rows correspond to δ = 0 and 90º respectively.
bOw···AC distance; see Figure 1A for details of geometry
S5
Table S2 Cartesian coordinates for model compounds with water at MP2/6-311++G (d,
p) level of theory at two orientations δ = 0° and δ = 90°
(1) Benzene-Water at 0°
C 0.000000
C 0.000000
C 1.212621
C 2.425242
C 2.425242
C 1.212621
H 1.212621
H 3.366326
H 3.366326
H 1.212621
H -0.941085
H -0.941085
O 1.212621
H 2.103823
H 1.350413
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
3.300000
3.300000
3.300000
0.000000
1.400214
2.100321
1.400214
0.000000
-0.700107
3.186992
1.943549
-0.543335
-1.786777
-0.543335
1.943550
0.700107
1.055534
-0.249410
(2) Benzene-Water at 90°
C 0.000000
C 0.000000
C 1.212621
C 2.425242
C 2.425242
C 1.212621
H 1.212621
H 3.366326
H 3.366326
H 1.212621
H -0.941085
H -0.941085
O 1.212621
H 1.589300
H 0.835942
0.000000 0.000000
0.000000 1.400214
0.000000 2.100321
0.000000 1.400214
0.000000 0.000000
0.000000 -0.700107
0.000000 3.186992
0.000000 1.943549
0.000000 -0.543335
0.000000 -1.786777
0.000000 -0.543335
0.000000 1.943550
3.400000 0.700107
3.994156 1.352534
3.994156 0.047680
S6
(3) Imidazole-Water at 0°
C 0.000000 0.000000 0.000000
N 0.000000 0.000000 1.367310
C 1.312154 0.000000 1.782542
C 2.053974 0.000000 0.616412
N 1.231935 0.000000 -0.487725
H -0.814974 0.000000 1.963235
H 1.588525 0.000000 2.825836
H 3.130165 0.000000 0.518603
H -0.912668 0.000000 -0.578995
O 0.910010 -3.300000 0.647512
H 1.830863 -3.300000 0.378071
H 0.957272 -3.300000 1.605810
(4) Imidazole-Water at 90°
C 0.000000 0.000000 0.000000
N 0.000000 0.000000 1.367310
C 1.312154 0.000000 1.782542
C 2.053974 0.000000 0.616412
N 1.231935 0.000000 -0.487725
H -0.814974 0.000000 1.963235
H 1.588525 0.000000 2.825836
H 3.130165 0.000000 0.518603
H -0.912668 0.000000 -0.578995
O 0.910010 -3.200000 0.647512
H 1.346915 -3.794156 0.033784
H 0.473383 -3.794156 1.261439
(5) Indole 5-membered ring-Water at 0°
N 0.000000
C 0.000000
C 1.362221
C 2.167412
C 1.300852
C -1.070657
C -0.757769
C 0.587260
C 1.645406
H -1.560895
0.000000 0.000000
0.000000 1.378068
0.000000 1.799459
0.000000 0.613009
0.000000 -0.461506
0.000000 2.285602
0.000000 3.642707
0.000000 4.085736
0.000000 3.182282
0.000000 4.374854
S7
H 0.792406 0.000000 5.152947
H 2.674505 0.000000 3.533718
H 3.247308 0.000000 0.552558
H 1.506869 0.000000 -1.523549
H -0.822981 0.000000 -0.583350
H -2.103906 0.000000 1.946266
O 0.978024 -3.200000 0.651156
H 1.005409 -3.200000 -0.307916
H 1.904265 -3.200000 0.901449
(6) Indole 5-membered ring-Water at 90°
N
C
C
C
C
C
C
C
C
H
H
H
H
H
H
H
O
H
H
0.000000 0.000000 0.000000
0.000000 0.000000 1.378068
1.362221 0.000000 1.799459
2.167412 0.000000 0.613009
1.300852 0.000000 -0.461506
-1.070657 0.000000 2.285602
-0.757769 0.000000 3.642707
0.587260 0.000000 4.085736
1.645406 0.000000 3.182282
-1.560895 0.000000 4.374854
0.792406 0.000000 5.152947
2.674505 0.000000 3.533718
3.247308 0.000000 0.552558
1.506869 0.000000 -1.523549
-0.822981 0.000000 -0.583350
-2.103906 0.000000 1.946266
0.978024 -3.200000 0.651156
0.528767 -3.794154 0.046409
1.427563 -3.794154 1.255693
(7) Indole 6-membered ring-Water at 0°
N 0.000000
C 0.000000
C 1.362221
C 2.167412
C 1.300852
C -1.070657
C -0.757769
C 0.587260
0.000000 0.000000
0.000000 1.378068
0.000000 1.799459
0.000000 0.613009
0.000000 -0.461506
0.000000 2.285602
0.000000 3.642707
0.000000 4.085736
S8
C
H
H
H
H
H
H
H
O
H
H
1.645406 0.000000 3.182282
-1.560895 0.000000 4.374854
0.792406 0.000000 5.152947
2.674505 0.000000 3.533718
3.247308 0.000000 0.552558
1.506869 0.000000 -1.523549
-0.822981 0.000000 -0.583350
-2.103906 0.000000 1.946266
0.325781 -3.200000 2.714745
0.379188 -3.200000 3.672720
-0.618235 -3.200000 2.543272
(8) Indole 6-membered ring-Water at 90°
N
C
C
C
C
C
C
C
C
H
H
H
H
H
H
H
O
H
H
0.000000 0.000000
0.000000 0.000000
1.362221 0.000000
2.167412 0.000000
1.300852 0.000000
-1.070657 0.000000
-0.757769 0.000000
0.587260 0.000000
1.645406 0.000000
-1.560895 0.000000
0.792406 0.000000
2.674505 0.000000
3.247308 0.000000
1.506869 0.000000
-0.822981 0.000000
-2.103906 0.000000
0.325781 -3.300000
0.824327 -3.894154
-0.173028 -3.894154
0.000000
1.378068
1.799459
0.613009
-0.461506
2.285602
3.642707
4.085736
3.182282
4.374854
5.152947
3.533718
0.552558
-1.523549
-0.583350
1.946266
2.714745
3.279548
2.150175
(9) Phenol-Water at 0°
C
C
C
C
C
C
0.000000
0.000000
1.209276
2.417149
2.428543
1.215380
0.000000 0.000000
0.000000 1.400059
0.000000 2.104553
0.000000 1.402202
0.000000 0.001399
0.000000 -0.694596
S9
O -1.153816 0.000000 2.140739
H 1.185495 0.000000 3.190055
H 3.353205 0.000000 1.954308
H 3.369824 0.000000 -0.539666
H 1.207813 0.000000 -1.781264
H -0.942835 0.000000 -0.544061
H -1.903059 0.000000 1.536241
O 1.212436 -3.300000 0.700059
H 1.350227 -3.300000 -0.249458
H 2.103637 -3.300000 1.055486
(10) Phenol-Water at 90°
C
C
C
C
C
C
O
H
H
H
H
H
H
O
H
H
0.000000
0.000000
1.209276
2.417149
2.428543
1.215380
-1.153816
1.185495
3.353205
3.369824
1.207813
-0.942835
-1.903059
1.212436
0.835908
1.589267
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
0.000000
-3.300000
-3.894154
-3.894154
0.000000
1.400059
2.104553
1.402202
0.001399
-0.694596
2.140739
3.190055
1.954308
-0.539666
-1.781264
-0.544061
1.536241
0.700059
0.047543
1.352399
(11) Protonated Imidazole-Water at 0°
C 0.000000
N 0.000000
C 1.256490
N 2.062306
C 1.317948
H 3.076325
H 1.768332
H -0.908944
H 1.560596
H -0.826255
0.000000 0.000000
0.000000 1.376639
0.000000 1.841304
0.000000 0.771174
0.000000 -0.386859
0.000000 0.820998
0.000000 -1.367235
0.000000 -0.581249
0.000000 2.877038
0.000000 1.966545
S10
O
H
H
0.930742 -3.200000
0.041647 -3.200000
1.488808 -3.200000
0.718369
0.357701
-0.062100
(12) Protonated Imidazole-Water at 90°
C 0.000000 0.000000 0.000000
N 0.000000 0.000000 1.376639
C 1.256490 0.000000 1.841304
N 2.062306 0.000000 0.771174
C 1.317948 0.000000 -0.386859
H 3.076325 0.000000 0.820998
H 1.768332 0.000000 -1.367235
H -0.908944 0.000000 -0.581249
H 1.560596 0.000000 2.877038
H -0.826255 0.000000 1.966545
O 0.930742 -2.900000 0.718369
H 0.207164 -3.494156 0.928091
H 1.654224 -3.494156 0.508318
Table S3 Absolute energies (in Hartree) at the MP2/G-311++G (d, p) level of theory
System
Benezene
Imidazole
Indole 5-membered ring
Indole 6-membered ring
Phenol
Protonated Imidazole
δ = 0°
-307.8614683
-301.9169059
-439.1052999
-439.1053391
-382.943905
-302.2900926
S11
δ = 90°
-307.8594534
-301.9154244
-439.1039655
-439.1030596
-382.9419516
-302.2984328