S1
Supporting Information for
“New Insights into α-GalNAc-Ser Motif: Influence of Hydrogen Bonding versus Solvent Interactions on the Preferred Conformation”
submitted to The Journal of the American Chemical Society by: Francisco Corzana, Jesús H. Busto, Gonzalo Jiménez-Osés, Juan L. Asensio, Jesús J. Barbero, Jesús M. Peregrina, * and Alberto Avenoza*
1
H and
13
1
C NMR spectra for compounds 1, 2, 3, 5α, and 6α ( H for 1 in natural abundance), and COSY
and HSQC correlations for compounds 1, 5α, and 6α. S2-S10 NOE data for 1 in natural abundance. S11 Comparison of the most relevant dihedral angles obtained from the unrestrained MD (MDH2O) and the MD-tar (MDH2O-tar) in explicit water simulations for compound 1. S12 B3LYP/6-31G(d) distances, dihedral angles, energy, enthalpy, free energy, entropy and coordinates of the optimized structure of 1 together with water molecules. S13-S18 1D-Selective HMQC-type experiments. S19 MPEG movie of the MD-tar trajectory (5 ps) in explicit water showing one bridging water molecule. S20
S2
1
H and 13C NMR spectra for compounds 1, 2, 3, 5α and 6α, and COSY and HSQC
correlations for compounds 1, 5α and 6α
H2s
O H1s Me3
15
O
H2O Me1
N
H3
N
Hα
HβproS + H3s + H5s Hα
HβproR H2s
H4s
O
2H6s
Figure S1. 1H and 13C NMR (D2O) spectra for 1.
H6s H3s H5s HβproR
H4s H6s
HβproS
O
H1s
O
N
13C
H1
OH OH OH
H2
Me2
1
Me1
Me2
Me3
S3
(D2O, 400 MHz)
H2s
O H1s Me3
H2O Me1
H3s + H5s HβproS
O
N O
H3
O
C
N H1
H3s H6s H5s HβproR
H4s H6s
HβproS H2
N
Hα O
HβproR
OH OH OH
Me1
Me2
Me2
1
H1s Hα
H4s H2s
2H6s
(H2O/D2O, 500 MHz)
Figure S2. 1H (D2O, 400 MHz) and (H2O/D2O, 500 MHz) spectra for 1 in natural abundance.
Me3
S4
OH OH O HO 15 NHAc
13
O
CONHMe NHAc
1
Figure S3. COSY and HSQC correlations for 1.
S5
HO 13
CONHMe
NHBoc 2
Figure S4. 1H and 13C NMR spectra for 2.
S6
OH 13
CONHMe
NHAc 3
Figure S5. 1H and 13C NMR spectra for 3.
S7
BnO OBn O BnO 15
NO2
13
O 5α
Figure S6. 1H and 13C NMR spectra for 5α.
CONHMe NHAc
S8
BnO OBn O BnO 15
NO2
13
O 5α
CONHMe NHAc
Figure S7. COSY and HSQC correlations for 5α.
S9
BnO OBn O BnO 15 NHAc
13
O
CONHMe NHAc
6α
Figure S8. 1H and 13C NMR spectra for 6α.
S10
BnO OBn O BnO 15 NHAc
13
O
CONHMe NHAc
6α
Figure S9. COSY and HSQC correlations for 6α.
S11
Figure S10. Selective ge-1D NOESY for Me3 in compound 1 (natural abundance). H1s-Hα H1s-H2s H1s-HβproR H1s-HβproS
6
5
NOE %
4
3
2
1
0 0
400
800
1200
1600
mixing time ms
Figure S11. NOE build-up curves for compound 1 in natural abundance.
S12
MDH2O
MDH2O-tar
Figure S12. Comparison of the Φp/Ψp, Φs/Ψs and χ1 distributions obtained from the 40 ns unrestrained MD (MDH2O) and 4 ns MDH2O-tar simulations for 1.
S13
1_gg_13_wat
1_ gt_15_wat
1_gg_12_wat
1_gg
1_gg_11_wat
1_ gg_1_wat
Figure S13. B3LYP/6-31G(d) geometries of different structures studied in this work. Minimizations of compound 1 include surrounding water molecules for the two major conformers of the hydroxymethyl group experimentally detected (gg and gt). As can be seen in these plots and in Table S1, the geometry of the solute significantly changes when decreasing the number of solvating water molecules. When the bridging water molecule is removed (1_gg_11_wat and 1_gg), the carbohydrate and peptide moieties tend to form an intramolecular hydrogen bond, which is not experimentally observed.
S14 Table S1. Some geometrical values for the optimized geometries obtained at B3LYP/6-31G(d) level.a
a
Φp
Ψp
χ1p
N3−O1
H3−O1
N3−H3−O1
H2s−C2s−N3−H3
1_gg_13_wat
−141.6
156.8
56.5
4.90
4.06
32.1
−174.3
1_gg_12_wat
−149.8
153.6
48.6
4.44
3.72
40.1
−178.1
1_gg_11_wat
−170.9
164.5
64.6
3.63
2.79
30.1
−165.9
1_gg_1_wat
−95.4
146.3
50.6
4.14
3.53
46.9
−172.9
1_gg
−152.0
153.1
62.1
3.18
2.23
17.2
−167.0
1_gt_15_wat
−161.8
173.5
70.0
4.52
3.71
34.1
−175.8
Distances are given in Å and angles in degrees.
Table S2. B3LYP/6-31G(d) energies, enthalpies, free energies, and entropies of the structures considered in this work.
1_gg_13_wat
E (Hartree)a -2308.23459022
H (Hartree)b -2307.421368
S (cal·mol–1 K–1)b 324.7
G (Hartree)b -2307.575652
Lowest freq. (cm–1) 14.5
1_gg_12_wat
-2231.80855456
-2231.023282
309.7
-2231.170416
16.6
1_gg_11_wat
-2155.37147238
-2154.615027
303.5
-2154.759247
14.3
1_gg_1_wat
-1391.03621528
-1390.561679
204.0
-1390.658600
15.1
1_gg
-1314.60292189
-1314.156883
191.2
-1314.247728
18.6
1_gt_15_wat
-2461.09599094
-2460.226211
347.084
-2460.391122
15.3
1 Hartree = 627.5 Kcal·mol–1. bThermal corrections at 298.15 K.
a
S15 Coordinates of optimized structures Structure 1_gg_13_wat (B3LYP/6-31G(d)) O C C H H H N H C C O N C H H H H H C H H O C H O C C O H H H H C O H H C O H H C H N H C C H H H O O H H O H H O H H O H H O H H O H H O H H
4.56904938 3.71004938 3.71304938 4.63704938 3.72604938 2.85704938 2.75804938 2.08504938 2.64004938 2.25804938 1.65904938 2.60804938 2.28604938 1.60104938 3.19804938 1.81204938 3.12104938 3.62304938 1.70104938 1.62504938 2.14704938 0.40904938 -0.52095062 -0.66595062 -0.02495062 0.23204938 0.94704938 2.21204938 2.09104938 0.31404938 1.14404938 0.92904938 -1.05995062 -1.95695062 -1.96495062 -0.78995062 -1.70495062 -2.94395062 -3.39095062 -1.03695062 -1.85795062 -2.55095062 -2.41295062 -1.85395062 -3.63795062 -4.09895062 -3.26695062 -4.73195062 -4.69995062 -4.39595062 -6.36095062 -5.91695062 -6.09395062 -2.00895062 -1.31495062 -2.86795062 2.92304938 3.22204938 3.71804938 -4.37495062 -4.34395062 -4.63695062 -4.88195062 -4.79995062 -4.07195062 5.05804938 4.83404938 5.22904938 5.34504938 5.19804938 6.28704938
0.11806481 0.75106481 0.72506481 1.19306481 -0.31693519 1.24606481 1.49306481 1.98306481 1.59106481 3.01106481 3.81306481 3.28606481 4.54306481 4.37306481 5.01306481 5.20406481 2.56706481 1.36906481 0.52806481 0.66006481 -0.45293519 0.60706481 -0.24093519 0.10506481 -1.55793519 -2.22393519 -3.51693519 -3.24693519 -2.72293519 -4.11993519 -4.09793519 -1.60393519 -2.37393519 -3.32993519 -3.32993519 -2.71993519 -0.97093519 -1.16993519 -0.31693519 -0.36893519 -0.25193519 -0.83293519 1.08606481 1.81406481 1.43506481 2.83806481 3.50906481 2.77806481 3.20706481 0.64106481 -0.28393519 0.07206481 -1.22893519 -3.34793519 -2.68093519 -2.86493519 -1.59193519 -2.21093519 -1.46393519 -2.03293519 -1.06393519 -2.34793519 -2.63393519 -3.58393519 -2.23893519 -1.05393519 -0.56193519 -1.97993519 -2.29493519 -1.38893519 -2.32593519
1.24499691 1.89299691 3.40499691 3.76299691 3.73899691 3.84099691 1.29999691 1.88499691 -0.14400309 -0.58600309 0.15799691 -1.84900309 -2.51000309 -3.34800309 -2.89100309 -1.78500309 -2.37500309 -0.56300309 -0.72900309 -1.81400309 -0.54700309 -0.12800309 -0.78200309 -1.81500309 -0.90700309 0.35699691 -0.01500309 -0.61500309 -1.43500309 -0.67700309 0.88999691 0.93599691 1.16699691 0.65199691 -0.34400309 2.17399691 1.34199691 1.99099691 2.23899691 1.97799691 -0.02000309 -0.63000309 0.10799691 0.57899691 -0.32600309 -0.00800309 0.21399691 0.88499691 -0.84200309 -0.93700309 0.95499691 0.15899691 0.95199691 -2.06300309 -2.19700309 -2.19700309 -2.84600309 -3.53200309 -2.25100309 -1.95200309 -1.83300309 -1.05700309 0.74299691 0.91499691 1.16099691 -1.31400309 -0.49800309 -0.96600309 2.36799691 2.01299691 2.59299691
O H H O H H O H H O H H O H H O H H
-4.62095062 -4.90695062 -5.36095062 5.01504938 5.13504938 4.04604938 1.20204938 1.49004938 1.48904938 -1.05295062 -0.31495062 -0.60095062 4.00104938 4.77004938 3.44004938 -5.96495062 -5.48395062 -6.86295062
0.82906481 0.72206481 0.44106481 -3.45793519 -3.20693519 -3.57693519 3.48206481 3.87106481 4.09706481 3.36206481 3.52606481 3.35006481 1.04606481 0.63506481 0.26306481 2.30406481 1.62206481 2.26406481
2.66899691 3.58799691 2.11699691 -0.16200309 0.78299691 -0.25700309 2.83299691 1.97599691 3.52399691 1.14299691 0.52799691 2.00799691 -3.12100309 -2.68400309 -3.30500309 -2.73400309 -2.22600309 -2.37100309
Structure 1_gg_12_wat (B3LYP/6-31G(d)) O C C H H H N H C C O N C H H H H H C H H O C H O C C O H H H H C O H H C O H H C H N H C C H H H O O H
4.24197771 3.24697771 2.93997771 3.70297771 3.00697771 1.95497771 2.41997771 1.54597771 2.54197771 2.07897771 1.23297771 2.65897771 2.31497771 2.18597771 3.10097771 1.38497771 3.35697771 3.59597771 1.78897771 1.74197771 2.33297771 0.48397771 -0.42502229 -0.58102229 0.07597771 0.30897771 1.01097771 2.33297771 2.31897771 0.41197771 1.10797771 1.00397771 -0.99902229 -1.91102229 -1.93302229 -0.75002229 -1.60802229 -2.85202229 -3.25402229 -0.92302229 -1.74802229 -2.49602229 -2.19502229 -1.57902229 -3.37202229 -3.68702229 -2.78302229 -4.29102229 -4.27202229 -4.19602229 -6.18002229 -5.73502229
0.30698089 0.86798089 0.70598089 1.23398089 -0.35601911 1.09198089 1.65398089 1.96698089 1.78998089 3.17798089 3.85098089 3.56998089 4.81398089 4.63398089 5.56698089 5.19498089 2.94998089 1.68198089 0.66298089 0.86398089 -0.27601911 0.56298089 -0.15901911 0.36298089 -1.42801911 -2.32901911 -3.54301911 -3.23101911 -2.51101911 -3.95301911 -4.31801911 -1.84401911 -2.61901911 -3.42101911 -3.18601911 -3.17901911 -1.27101911 -1.56001911 -0.76001911 -0.82801911 -0.28101911 -0.67101911 1.02998089 1.54298089 1.59098089 2.91298089 3.43898089 2.70198089 3.52598089 1.05098089 -0.24601911 0.26698089
1.76997134 2.27697134 3.74997134 4.33197134 4.00497134 4.02397134 1.56797134 1.99097134 0.12397134 -0.34602866 0.26497134 -1.49202866 -2.16302866 -3.23402866 -2.02602866 -1.74102866 -1.92002866 -0.13202866 -0.60102866 -1.67702866 -0.46002866 -0.04202866 -0.83902866 -1.79302866 -1.20202866 -0.08802866 -0.68402866 -1.11402866 -1.77902866 -1.50602866 0.08197134 0.60997134 0.65797134 -0.05502866 -1.02302866 1.56997134 1.12197134 1.72997134 2.16097134 1.86097134 -0.05902866 -0.75102866 0.38897134 1.02697134 0.06497134 0.72597134 1.04097134 1.61697134 0.03497134 -0.71302866 0.94497134 0.24097134
S16 H O H H O H H O H H O H H O H H O H H O H H O H H O H H O H H O H H
-5.96102229 -2.01102229 -1.25902229 -2.82202229 3.35597771 3.83497771 3.99497771 -4.28702229 -4.22702229 -4.57302229 -4.84402229 -4.84702229 -4.01802229 5.12197771 4.79597771 5.23597771 4.61897771 4.62797771 5.46697771 -4.39102229 -4.68602229 -5.15002229 4.90697771 4.76897771 4.00797771 -0.35102229 0.10697771 -0.63502229 4.42397771 5.09297771 3.90997771 -5.60402229 -5.19802229 -6.51602229
-1.17601911 -2.80701911 -2.19401911 -2.23501911 -1.14001911 -1.67401911 -1.04001911 -1.36601911 -0.44801911 -1.86501911 -2.56801911 -3.53501911 -2.34901911 -0.69001911 -0.24601911 -1.64301911 -2.25301911 -1.30801911 -2.39201911 0.36698089 0.07198089 0.15298089 -3.18901911 -3.02001911 -3.34901911 2.65198089 3.18398089 3.29598089 1.52198089 1.06898089 0.76498089 3.26998089 2.42498089 3.19698089
0.71697134 -2.70102866 -2.71002866 -2.72402866 -2.76702866 -3.42102866 -2.00402866 -2.29502866 -1.96702866 -1.49502866 0.17697134 0.11897134 0.68597134 -0.77902866 0.03097134 -0.48002866 2.74397134 2.46897134 3.19197134 2.84397134 3.71897134 2.22697134 0.11397134 1.07397134 -0.24502866 2.08097134 1.37797134 2.74697134 -2.60602866 -2.06002866 -2.95502866 -1.95102866 -1.67802866 -1.63302866
Structure 1_gg_11_wat (B3LYP/6-31G(d)) O C C H H H N H C C O N C H H H H H C H H O C H O C C O H H H H C O H H C O H H
4.51297368 3.63497368 3.67997368 4.59897368 3.72697368 2.82097368 2.61897368 1.90197368 2.39097368 1.27897368 0.55697368 1.16897368 0.14297368 -0.62102632 0.59497368 -0.33102632 1.81297368 3.31197368 1.95997368 1.89897368 2.69997368 0.69197368 -0.21402632 -0.34102632 0.25897368 0.49597368 1.18997368 2.48197368 2.40897368 0.56497368 1.34397368 1.20297368 -0.80902632 -1.74002632 -1.78802632 -0.55702632 -1.40002632 -2.63502632 -2.99702632 -0.69702632
0.97302961 1.63302961 1.79702961 2.32602961 0.80002961 2.33902961 2.22102961 2.75302961 2.09302961 3.09602961 3.57502961 3.34502961 4.21902961 3.64702961 4.93702961 4.75702961 2.87202961 2.32402961 0.67502961 0.60002961 -0.05197039 0.38902961 -0.24897039 0.34302961 -1.50097039 -2.44497039 -3.62497039 -3.25697039 -2.47497039 -4.01897039 -4.42497039 -1.98897039 -2.74597039 -3.51397039 -3.23397039 -3.33597039 -1.40397039 -1.69397039 -0.90197039 -0.99297039
1.50496711 2.09896711 3.60296711 3.87596711 4.05396711 4.00596711 1.44996711 1.93596711 0.02196711 -0.34703289 0.53596711 -1.66403289 -2.21403289 -2.75403289 -2.90603289 -1.39303289 -2.30703289 -0.52503289 -0.37203289 -1.45703289 -0.02803289 0.21896711 -0.65003289 -1.56603289 -1.08303289 -0.00703289 -0.67203289 -1.15203289 -1.73903289 -1.48303289 0.05796711 0.69796711 0.74596711 0.02096711 -0.93303289 1.63696711 1.26296711 1.88496711 2.36696711 2.00196711
C H N H C C H H H O O H H O H H O H H O H H O H H O H H O H H O H H O H H O H H O H H
-1.54202632 -2.30302632 -1.93702632 -1.21802632 -3.10002632 -3.26702632 -2.31002632 -3.69302632 -3.96002632 -4.00502632 -5.93402632 -5.51802632 -5.74202632 -1.91402632 -1.15102632 -2.71502632 3.33997368 3.78997368 4.05597368 -4.16502632 -4.10002632 -4.44502632 -4.69502632 -4.74802632 -3.84702632 5.19797368 4.99497368 5.21197368 4.71297368 4.81897368 5.58897368 -4.00802632 -4.26402632 -4.81702632 4.87097368 4.67597368 4.01297368 3.05397368 3.98097368 3.09597368 -5.47402632 -5.07002632 -6.35602632
-0.37997039 -0.73297039 0.94402961 1.47902961 1.56802961 2.93902961 3.46302961 2.80702961 3.52002961 1.03802961 -0.27097039 0.25802961 -1.19597039 -2.76997039 -2.17097039 -2.18597039 -0.91197039 -1.41597039 -0.72597039 -1.32097039 -0.41697039 -1.84997039 -2.58897039 -3.55497039 -2.41397039 -0.44897039 0.18802961 -1.33497039 -1.48097039 -0.59897039 -1.69197039 0.29602961 0.06202961 0.10402961 -2.78297039 -2.48697039 -3.05397039 1.81602961 2.09502961 0.83002961 3.26702961 2.41802961 3.23302961
0.11096711 -0.58603289 0.57496711 1.04996711 0.30296711 0.91496711 1.00696711 1.91796711 0.30296711 -0.38103289 1.31896711 0.61096711 1.04796711 -2.58903289 -2.60403289 -2.56703289 -2.79703289 -3.49403289 -2.10903289 -2.06403289 -1.70203289 -1.28103289 0.37396711 0.30596711 0.86196711 -0.96903289 -0.25803289 -0.50203289 2.78196711 2.35696711 3.13796711 3.09196711 3.99696711 2.53296711 0.29996711 1.21696711 -0.09403289 -3.32803289 -3.35503289 -3.27803289 -1.54003289 -1.27803289 -1.13903289
Structure 1_gg_1_wat (B3LYP/6-31G(d)) O C C H H H N H C C O N C H H H H H C H H O C H O C C O H H H
4.34395588 3.41295588 3.28995588 4.27495588 2.97095588 2.57295588 2.37895588 1.72795588 2.42495588 2.96595588 2.72795588 3.69395588 4.28295588 4.22495588 5.33195588 3.71795588 3.97595588 3.11795588 1.04695588 1.05795588 0.80295588 0.08895588 -1.14504412 -0.98904412 -1.78204412 -2.08204412 -2.50804412 -1.48404412 -1.31304412 -3.45404412 -2.67404412
-2.11200000 -1.58300000 -1.62000000 -1.43700000 -2.62200000 -0.89000000 -0.95600000 -0.38000000 -0.75800000 0.64300000 1.65200000 0.69600000 1.92700000 1.94200000 2.02700000 2.76600000 -0.17700000 -1.51200000 -0.99800000 -0.69700000 -2.06700000 -0.23600000 -0.04100000 0.45000000 -1.27300000 -2.08500000 -3.44100000 -3.99700000 -3.33400000 -3.33900000 -4.13800000
1.00407353 1.60207353 3.11607353 3.55307353 3.42507353 3.50407353 0.95307353 1.48007353 -0.47792647 -0.83492647 -0.16292647 -1.97592647 -2.48392647 -3.57592647 -2.17792647 -2.07692647 -2.40092647 -0.86492647 -1.11292647 -2.17092647 -1.06092647 -0.38892647 -1.03592647 -2.00592647 -1.35592647 -0.19392647 -0.74592647 -1.55692647 -2.24592647 -1.29792647 0.08107353
S17 H C O H H C O H H C H N H C C H H H O O H H
-1.16604412 -3.12004412 -4.34104412 -4.09004412 -3.39104412 -2.55804412 -3.53804412 -4.35404412 -1.72804412 -2.03804412 -2.89604412 -1.37404412 -0.60504412 -1.85204412 -1.11204412 -0.20904412 -1.78604412 -0.84604412 -2.80204412 1.00995588 1.63295588 1.36095588
-2.21800000 -1.34500000 -1.14700000 -0.90000000 -1.93000000 0.01700000 0.74000000 0.66200000 -0.15000000 0.82200000 1.13900000 2.03700000 1.96000000 3.26600000 4.44200000 4.14100000 4.95700000 5.15200000 3.42600000 1.55800000 1.68400000 2.10800000
0.39507353 0.64607353 -0.07592647 -0.98192647 1.53207353 1.09707353 1.81207353 1.28507353 1.79307353 -0.12192647 -0.72392647 0.28107353 0.94807353 -0.07492647 0.54607353 1.08607353 1.23807353 -0.24192647 -0.83692647 1.96807353 1.21007353 2.68407353
Structure 1_gg (B3LYP/6-31G(d)) O C C H H H N H C C O N C H H H H H C H H O C H O C C O H H H H C O H H C O H H C H N H C C H H H O
3.73903608 3.40303608 3.57803608 4.63003608 2.99603608 3.26803608 2.84403608 2.57903608 2.64703608 2.69303608 2.35703608 3.09103608 3.14703608 2.35303608 4.11803608 3.01903608 3.39203608 3.45103608 1.30903608 1.21403608 1.28903608 0.25603608 -0.92196392 -0.68196392 -1.74396392 -2.19096392 -2.91096392 -2.04996392 -1.69496392 -3.81396392 -3.22696392 -1.31096392 -3.04396392 -4.23296392 -3.98396392 -3.38596392 -2.22296392 -2.99296392 -3.79696392 -1.39096392 -1.65296392 -2.49196392 -0.79596392 0.13803608 -1.25596392 -0.27096392 0.75603608 -0.58196392 -0.31396392 -2.37496392
-2.96396907 -2.19696907 -2.53696907 -2.77496907 -3.43596907 -1.73396907 -0.97896907 -0.33296907 -0.51696907 1.02003093 1.66103093 1.59503093 3.03503093 3.37603093 3.32003093 3.51403093 0.99303093 -0.93496907 -1.00596907 -0.67796907 -2.10096907 -0.46296907 -0.07396907 0.40903093 -1.17796907 -1.95696907 -3.16496907 -3.91496907 -3.28096907 -2.83196907 -3.82996907 -2.30596907 -1.06396907 -0.61696907 -0.40896907 -1.62496907 0.15203093 1.00103093 1.21303093 -0.19796907 0.90003093 1.33503093 2.00903093 1.80403093 3.29903093 4.32703093 3.95103093 4.62203093 5.21903093 3.60503093
0.22702577 1.12402577 2.59502577 2.77902577 2.82102577 3.27002577 0.86202577 1.59302577 -0.49397423 -0.47997423 0.51802577 -1.64097423 -1.84297423 -2.51697423 -2.26097423 -0.87197423 -2.39397423 -1.11097423 -1.08597423 -2.13197423 -1.05997423 -0.29897423 -0.95897423 -1.91597423 -1.30597423 -0.16597423 -0.75697423 -1.59697423 -2.24197423 -1.28997423 0.05202577 0.38802577 0.73502577 0.07402577 -0.84297423 1.61202577 1.20902577 2.03002577 1.52302577 1.83102577 -0.02197423 -0.57297423 0.32702577 0.66802577 0.32502577 0.85802577 0.90502577 1.86702577 0.22702577 -0.07197423
Structure 1_gt_15_wat (B3LYP/6-31G(d)) O C C H H H N H C C O N C H H H H H C H H O C H O C C O H H H H C O H H C O H H C H N H C C H H H O O H H O H H O H H O H H O H H O H H O H H O H H O
-4.82100581 -4.76000581 -5.20000581 -4.35200581 -5.54500581 -5.99100581 -4.25800581 -4.32600581 -3.87800581 -3.79500581 -3.92500581 -3.58700581 -3.47100581 -4.25600581 -2.50000581 -3.57800581 -3.39000581 -4.65500581 -2.57600581 -2.48500581 -2.61900581 -1.43300581 -0.30200581 -0.50400581 0.03399419 0.38399419 0.69799419 1.54099419 2.50299419 1.11599419 -0.25000581 -0.49000581 1.53699419 2.77999419 2.79699419 1.62899419 1.31899419 2.50799419 3.26199419 0.54299419 0.87699419 1.70499419 0.56699419 -0.23900581 1.32399419 0.96199419 1.80999419 0.84199419 0.06199419 2.31799419 4.34399419 3.85399419 3.67899419 -1.58200581 -2.42700581 -1.74800581 -6.79100581 -6.14100581 -6.28500581 0.64099419 1.02299419 1.12099419 5.47099419 5.73699419 4.49099419 3.26599419 3.03499419 3.27299419 3.62499419 4.17499419 3.19899419 -2.75300581 -3.55800581 -2.73900581 -1.92000581
-2.04797674 -1.13297674 -1.32897674 -1.70897674 -0.39997674 -2.08297674 0.08402326 0.86602326 0.44302326 1.97502326 2.67102326 2.48302326 3.91902326 4.44202326 4.30102326 4.12202326 1.86702326 0.08402326 -0.20197674 -0.00497674 -1.28097674 0.34302326 0.36602326 0.94602326 -0.92297674 -1.91097674 -3.21097674 -3.06197674 -2.99997674 -3.93797674 -3.61297674 -2.10897674 -1.41597674 -1.50897674 -0.98197674 -2.08597674 0.02102326 0.49502326 0.43502326 -0.00097674 0.96702326 1.06502326 2.30302326 2.42602326 3.37602326 4.67302326 4.96402326 5.45502326 4.59602326 3.33602326 3.07002326 3.36002326 2.53502326 3.04702326 3.01702326 2.50302326 -3.89197674 -3.35797674 -4.67797674 -1.69297674 -2.11897674 -2.08597674 -1.83797674 -2.17997674 -1.89297674 -1.43497674 -0.69297674 -1.03997674 0.00602326 0.44402326 0.73802326 -3.51197674 -3.15797674 -3.13097674 -1.82597674
-0.97000291 -1.80800291 -3.24500291 -3.83000291 -3.70800291 -3.26800291 -1.49500291 -2.13700291 -0.14100291 -0.05600291 -1.08300291 1.16299709 1.37099709 0.81799709 1.03199709 2.43899709 1.96799709 0.54699709 0.32799709 1.39699709 0.17299709 -0.35200291 0.48799709 1.39599709 0.98399709 -0.00900291 0.75799709 1.88999709 1.66199709 0.04799709 1.12199709 -0.64400291 -0.88700291 -0.21100291 0.62699709 -1.74900291 -1.42500291 -2.06100291 -1.40700291 -2.19600291 -0.29200291 0.41199709 -0.77700291 -1.40900291 -0.50000291 -1.19100291 -1.82100291 -0.43500291 -1.80300291 0.26599709 -1.77300291 -0.97600291 -2.24000291 -2.51700291 -2.01300291 -3.30100291 -1.95300291 -1.45400291 -2.21200291 4.05199709 3.23699709 4.79499709 -0.62700291 -1.51800291 -0.64300291 -3.90500291 -3.29400291 -4.79000291 1.86699709 1.17299709 2.36499709 0.77899709 0.36299709 1.67799709 3.01899709
S18 H H O H H O H H O H H O H H O H H O H H
-1.24000581 -1.35000581 4.72699419 5.04199419 5.30199419 4.28899419 4.88899419 4.22899419 0.01299419 0.31799419 0.76999419 -2.71300581 -2.69900581 -1.77000581 5.70099419 4.84499419 5.57199419 2.35399419 2.32199419 2.83399419
-2.00397674 -1.54497674 0.71702326 1.52902326 -0.07397674 -2.72997674 -2.73197674 -1.77997674 1.07502326 0.14402326 1.57602326 0.95202326 -0.02897674 1.17102326 -2.56397674 -2.15597674 -3.51497674 2.29802326 2.72902326 2.91302326
3.70299709 2.27599709 -0.48600291 -0.94300291 -0.66100291 1.99999709 1.23099709 2.22799709 3.88799709 3.95699709 3.52699709 3.44299709 3.46199709 3.63499709 -3.24900291 -3.53100291 -3.38000291 2.78199709 1.88899709 3.35699709
Ac
2
N H
C2s
JH-CO
C
NHMe
Cα
Figure S14. 1D-Selective HMQC-type experiments with the period of evolution of coupling (1/2J) chosen to match J values of 1, 2, 3, 4 and 5 Hz.
O
13
S19
MPEG movie of the MD-tar trajectory (5 ps) in explicit water showing one bridging water molecule
S20
Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, and J. A. Pople, Gaussian, Inc., Wallingford CT, 2004.
B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M.
C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B.
Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M.
X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C.
Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene,
Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A.
Gaussian 03, Revision C.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T.
Reference 30
Kollman, P.A. (1999), AMBER 6, University of California, San Francisco.
Cheng, A. L.; Vincent, J. J.; Crowley, M.; Tsui, V.; Radmer, R. J.; Duan, Y.; Pitera, J.; Massova, I.; Seibel, G. L.; Singh, U. C.; Weiner, P. K.;
Case, D. A.; Pearlman, D. A.; Caldwell, J. W.; Cheatham, T. E., III; Ross, W. S.; Simmerling, C. L.; Darden, T. A.; Merz, K. M.; Stanton, R. V.;
Reference 16b
Complete references 16b and 30.
S21
