suppmat1515.doc 1074KB Jun 05 2011 09:30:54 PM

(1)

Development of a Polarizable Force Field For Proteins via

Ab

Initio

Quantum Chemistry: First Generation Model and Gas

Phase Tests

George A. Kaminski, Harry A. Stern, B. J. Berne, and Richard A. Friesner

Department of Chemistry, Columbia University, New York, New York 10027

Yixiang X. Cao, Robert B. Murphy, Ruhong Zhou, and Thomas A. Halgren,

Shrödinger, Inc., 120 West 45th_{Street, Tower 45, 8}th_{Floor, New York, NY 10036}

Supporting Materials

Listed below are parameters for all the dipeptides, also used in the alanine tetrapeptide and PDB proteins. Values for the parameters that are not listed (bond stretching, angle bending, some torsional parameters) are taken directly from the OPLS-AA (Jorgensen, W.L.; Maxwell D.S.; TiradoRives, J. J. Am. Chem. Soc., 1996, 113, 11225-11236).

(2)

(3)

(4)

(5)

(6)

Table S1. Lennard-Jones Parameters

Atom , Å , kcal/mol

CT, CT1, CP1 3.50 0.066

C, CG1, CO3 3.75 0.105

HC 2.50 0.030

N 3.30 0.280

O 3.16 0.280

OH 3.25 0.280

CA, CR, CV, CW, C*, CB9, CN, CX 3.55 0.070

HA 2.42 0.030

SH, S 3.60 0.425

NA, NB 3.25 0.170

OH6 3.20 0.190

O2 2.96 0.210

N3A 3.00 0.080

NA, protonated histidine 3.05 0.160

CA8 2.25 0.050

N2 3.20 0.100

Table S2. Torsional Parameters, kcal/mol

Angle V1 V2 V3

Alanine and all backbones

C-N-CT1-CT -2.485 1.191 -0.773

C-CT1-N-C -0.330 -1.113 1.276

N-C-CT1-N -6.976 2.821 -0.613

CT-CT1-C-N -3.642 0.519 0.382

Serine

N-CT1-CT-OH -2.165 1.510 0.580

CT1-CT-OH-HO 1.502 -1.728 1.581

C-CT1-CT-OH -4.700 -1.110 0.194

Phenylalanine

CA-CA-CT-CT1 -0.530 0.519 -1.744

C-CT1-CT-CA 1.315 0.578 -0.741

CA-CT-CT1-N -2.221 2.173 -0.301

Cysteine

N-CT1-CT-SH -6.995 1.715 -0.860

CT1-CT-SH-HS -1.201 -1.809 0.832

C-CT1-CT-SH -6.647 -0.703 0.962

Asparagine

C-CT-CT1-N 5.632 3.182 4.353

CT1-CT-C-N -3.060 -0.115 -0.418

C-CT-CT1-C -2.114 0.935 -2.618

Glutamine

CT-CT-CT1-N 3.925 0.958 -3.374

(7)

C-CT1-CT-CT 0.539 1.424 4.422

CT-CT-C-N -0.471 -0.431 -0.078

Histidine

CV-CT-CT1-N -1.116 0.691 -0.173

CT1-CT-CV-NB 0.061 0.231 -0.362

CT1-CT-CV-CW 0.000 0.000 0.000

C-CT1-CT-CV -1.944 -0.466 0.012

Leucine

CT-CT-CT1-N 5.246 0.874 -2.843

C-CT1-CT-CT 1.509 0.255 2.827

CT-CT-CT-CT1 0.335 0.302 0.141

Isoleucine

CT-CT-CT1-N -5.102 2.334 1.578

C-CT1-CT-CT -6.975 2.498 -0.597

CT-CT-CT-CT1, CT-CT-CT-CT 1.888 -0.269 0.591

Valine

CT-CT-CT1-N -6.039 1.446 0.286

C-CT1-CT-CT -2.690 0.846 0.271

Methionine

CT-CT-CT1-N -12.673 0.981 -2.634

CT1-CT-CT-S -0.430 0.135 -0.173

C-CT1-CT-CT -2.883 1.175 2.906

CT-CT-S-CT -2.184 -2.478 1.612

Tryptophan

C*-CT-CT1-N -1.493 1.386 -1.883

CT1-CT-C*-CW -1.380 0.572 0.048

CB9-C*-CT-CT1 0.000 0.000 0.000

C-CT1-CT-C* -1.079 0.419 1.849

Threonine

N-CT1-CT-OH -9.964 0.906 -2.414

CT1-CT-OH-HO 1.502 -1.728 1.581

C-CT1-CT-OH -16.848 0.682 1.346

Tyrosine

CA-CT-CT1-N 0.283 1.336 -3.733

CA-CA-CT-CT1 0.000 0.000 0.000

C-CT1-CT-CA -0.917 0.517 3.706

CA-CA-OH6-HO 0.000 3.943 0.000

Aspartic Acid

CG1-CT-CT1-N 3.712 1.813 0.301

CT1-CT-CG1-O2 0.000 0.695 0.000

C-CT1-CT-CG1 -3.900 4.331 -0.822

Glutamic Aced

CT-CT-CT1-N -1.513 0.871 0.963

CO3-CT-CT-CT1 -3.404 0.201 0.117

CT-CT-CO3-O2 0.000 0.820 0.000

(8)

Lysine

CT-CT-CT1-N -3.264 -0.211 0.430

C-CT1-CT-CT -1.027 -0.426 0.133

CT-CT-CT-N3A 2.144 -1.352 2.069

Protonated Histidine

CX-CT-CT1-N -5.864 1.304 -0.513

CT1-CT-CX-NA -0.139 -0.558 -1.320

CT1-CT-CX-CX 0.000 0.000 0.000

C-CT1-CT-CX -1.000 0.272 1.133

Agrinine

CT-CT-CT1-N 2.359 0.813 -0.568

CT-CT-CT-CT1 -0.775 0.807 -1.792

CT-CT-CT-N2 0.673 0.987 -2.000

CA8-N2-CT-CT -1.697 0.542 0.542

C-CT1-CT-CT 2.416 -0.689 1.860

Tables S3 and S4 list electrostatic parameters. Please note that we used a

scaling factor of 1.0 for the electrostatic 1,4-interactions, unlike the 0.5 value

for the van-der-Waals ones.

For the fixed bond charge increments – as an example – O236_X0 bci value of 0.326463 means an electron transfer from O to X (negative resulting charge on X)

Dipole  means internal electrostatic field, resulting in a point “permanent dipole” located on the first atom in the pair, dipole  means internal electrostatic field, resulting in a point “permanent dipole” located on the second atom in the pair. A positive  value means field producing a dipole directed toward the other atom in the pair, a negative value – away from the other atom.

Table S3. Fixed Bond Charge Increments, in e, and Dipole s, in (kcal/mol)1/2_·Å-3/2_.

Atom Pair Bond Charge Increment Dipole  /  Alanine

C135_C224 0.097985 0.607132 / 0.116592

C135_C235 -0.0480366 0.153272 / 0.373441

C135_H140 -0.110953 0.755875 /

-C224_C235 -0.00735223 -0.152324 / 0.279954

C224_H140 -0.209973 2.04571 /

-C224_N238 0.208593 1.63831 / 0.396263

C235_N238 -0.0327599 0.64934 / -0.0116159

C235_O236 0.227873 1.56473 /

-C242_H140 -0.0998559 0.379682 /

-C242_N238 0.220074 0.273629 / 0.0340511

H241_N238 0.258316 - / 0.56991

(9)

-Serine

C157_C224 0.116725 2.18762 / -0.131951

C157_H140 -0.136309 0.608399 /

-C157_O154 -0.110053 0.643742 / -1.97661

H155_O154 0.122747 -6.441 / -8.67218

O154_X0 0.600477

-Phenylalanine

C145_C149 -0.0673306 0.000229846 / -0.000239204

C145_H146 -0.102698 0.000403568 /

-C149_C224 0.0200496 -0.00005505 / 0.00123112

C149_H140 -0.0596082 0.000327497 /

-C145_C145 - -0.000633269

Cysteine

C206_C224 -0.0534597 0.00563573 / -0.00236531

C206_H140 -0.109281 0.0153869 /

-C206_S200 0.0903085 -0.020398 / -0.00595555

H204_S200 0.130253 - / 0.00719557

S200_X0 0.017169

-Asparagine

C136_C224 0.196372 0.977204 / -1.89449

C136_C235 -0.13411 -0.237043 / 1.45552

C136_H140 -0.097974 0.418817 /

-C235_N237 -0.102893 0.370868 / 3.17608

C235_O236 (side chain) 0.273747 0.634036 /

-H240_N237 0.407637 - / -0.298673

O236_X0 (side chain) 0.240195

-Glutamine

C136_C224 0.0437679 0.0013247 / 0.00270597

C136_C235 0.164519 -0.00533217 / 0.0133523

C136_H140 0.0337042 0.000494025 /

-C235_N237 -0.196311 0.011942 / -0.00849117

C235_O236 (side chain) 0.480364 0.0241726 /

-H240_N237 0.199717 - / 0.00956328

O236_X0 (side chain) 0.120912

-C136_C136 - 0.00306502

Histidine

C224_C505 0.0100364 0.00107392 / 0.00139211

C505_C507 0.0599774 -0.00551098 / -0.00017132

C505_H140 -0.0641425 0.00456435 /

-C506_H146 -0.114389 0.0052744 /

-C506_N503 -0.131173 0.00644356 / -0.00586025

C506_N511 0.191382 -0.0120094 / 0.00528713

C507_C508 -0.160069 0.000912032 / -0.0106541

C507_N511 0.0813819 -0.000800828 / 0.00207551

C508_H146 -0.102242 0.00826427 /

(10)

H504_N503 0.161869 - / 0.00916099 Leucine

C135_C137 -0.146868 0.033175 / 0.000333922

C136_C137 -0.124146 0.000621941 /0.0000245489

C136_C224 0.0166872 -0.000208909 / -0.00630183

C136_H140 -0.0678362 0.000535165 /

-C137_H140 0.116302 0.000450057 /

-Isoleucine

C135_C136 0.0 0.0 / 0.0

C135_C137 -0.146868 0.033175 / 0.000333922

C136_C137 -0.124146 0.000621941 / 0.0000245489

C136_C224 0.0166872 -0.000208909 / -0.00630183

C136_H140 -0.0678362 0.000535165 /

-C137_C224 0.0 0.0 / 0.0

C137_H140 0.116302 0.000450057 /

-Valine

C135_C137 0.0723389 1.23919 / 0.148709

C137_C224 0.104525 -0.0868066 / -0.229779

C137_H140 -0.00657239 0.0740794 /

-Methionine

C136_C210 0.0935418 1.38705 / 0.444529

C136_C224 0.0208381 0.801983 / 0.810454

C136_H140 -0.162903 2.42772 /

-C209_H140 -0.243665 0.291426 /

-C209_S202 -0.155553 0.0724554 / 0.802467

C210_H140 -0.125907 0.317935 /

-C210_S202 0.0600352 -0.151669 / -1.37233

S202_X0 0.449691

-Proline

C136_C245 0.0729211 0.635282 / -0.233324

C136_C246 0.0957254 0.163052 / 0.216856

C136_H140 -0.0532278 0.996827 /

-C235_C246 -0.0176697 0.0542661 / -0.073014

C235_N239 -0.0136698 1.0433 / 0.278585

C245_H140 -0.0116227 0.321562 /

-C245_N239 0.26151 0.603253 / 0.288494

C246_H140 -0.0779027 0.613241 /

-C246_N239 0.201598 0.52365 / -0.668299

C136_C136 - 0.234194

Tryptophan

C136_C224 -0.00548767 0.000517722 / -0.000759049

C136_C500 0.0528376 -0.00284223 / 0.000798661

C136_H140 -0.0265289 0.00261878 /

-C145_C501 -0.00191486 0.00572442 / -0.000158477

C145_C502 0.0173216 -0.0015452 / -0.00160748

(11)

-C500_C501 0.0772466 -0.00130709 / 0.000248156

C500_C514 -0.0572644 0.000327291 / -0.0000533602

C501_C502 -0.0224854 -0.0000905563 / -0.00552142

C502_N503 -0.164221 0.00678851 / -0.0165872

C514_H146 -0.063842 0.0000442391 /

-C514_N503 -0.0521954 0.00000607413 / -0.0061889

H504_N503 0.241869 - / 0.0196599

C145_C145 - -0.00465174

Threonine

C135_C158 0.112878 1.14045 / 0.737352

C158_C224 0.0992506 1.98056 / 0.588577

C158_H140 -0.204639 2.43919 /

-C158_O154 -0.10328 -0.308812 / 3.56155

H155_O154 0.316595 -1.58336 / -3.89152

O154_X0 0.239077

-Tyrosine

C145_C149 -0.00579876 -0.00000790066 / -0.00221347

C145_C166 -0.0304862 0.00000958763 / -0.00378592

C145_H146 -0.121312 0.0000371821 /

-C149_C224 0.0154813 -0.00019629 / 0.00140221

C149_H140 -0.0160531 0.00271868 /

-C166_O167 0.0325574 0.00219646 /

-H168_O167 0.254649

-O167_X0 0.159654

-C145_C145 - -0.0000376123

Aspartic Acid. Formal charge of –0.5 on O272

C224_C274 -0.0977027 0.00507626 / -0.00648952

C271_C274 0.0304503 0.000875131 / 0.00783434

C271_O272 0.1368 -0.000819109 / 0.00660001

C274_H140 0.0696202 0.00140657 /

-O272_X0 0.0748858

-Glutamic Acid. Formal charge of –0.5 on O272

C136_C224 0.0786512 -0.00324192 / 0.00701377

C136_C274 -0.0825442 0.0122969 / 0.0212826

C136_H140 -0.0606561 0.0103197 /

-C271_C274 0.143842 -0.135622 / -0.0297912

C271_O272 0.171253 0.124577 /

-C274_H140 0.0288231 0.0071406 /

-O272_X0 0.125131

-Lysine. Formal charge of +1.0 on N287

C136_C224 0.00763358 -0.024419 / -0.0851402

C136_C292 0.0604499 -0.0659708 / -0.053823

(12)

-C292_H140 -0.0282786 0.03601 /

-C292_N287 0.397861 0.0180809 / 0.114811

H290_N287 0.341731 - / -0.113318

C136_C136 - 0.244323

Protonated Histidine. Formal charge of +0.5 on N512

C224_C505 -0.0298412 0.32426 / 0.884187

C505_C510 0.185721 0.106838 / 0.0102203

C505_H140 -0.15159 1.10232 /

-C509_H146 -0.230999 0.0178131 / -

C509_N512 0.0689035 -0.0214623 / -0.0158379

C510_H146 -0.103774 0.0273401 /

-C510_N512 0.155405 0.0286613 / -0.0193385

H513_N512 0.297322 - / 0.0208468

C510_C510 - -0.0858125

Arginine. Formal charge of +1.0 on C302

C136_C224 -0.00283199 0.000661955 / -0.000863189

C136_C308 -0.0342771 0.00201562 / -0.00164835

C136_H140 0.0592934 0.00287667 /

-C302_N300 -0.10473 0.000889051 / -0.00918126

C302_N303 0.00782999 -0.00082715 / -0.000867548

C307_C308 -0.0918754 0.00793005 / -0.00502689

C307_H140 0.092882 0.0117669 /

-C307_N303 -0.0280027 0.00315085 / -0.00211463

C308_H140 -0.0876708 0.00743096 /

-H301_N300 0.217723 - / 0.00991513

H304_N303 0.0997339 - / 0.00312121

Table S4. Inverse Polarizabilities, Å-3

(13)

(14)