suppmat1587.doc 89KB Jun 05 2011 09:30:54 PM

Molecular Dynamics Simulations of the

Dinuclear Zinc-



-Lactamase from

Bacteroides fragilis

Complexed with Imipenem

Dimas Suárez, Natalia Díaz, and Kenneth M. Merz, Jr.*

Supplementary Material

AMBER representation for Imipenem

HF/6-31G*

optimized geometry

charges

RESP

Atom

Type

ATOM 1 N1 IMI 1 1.728 0.250 -0.486

ATOM 2 C2 IMI 1 3.050 0.522 -0.114 ATOM 3 O3 IMI 1 3.781 1.434 -0.275 ATOM 4 C4 IMI 1 3.228 -0.861 0.515 ATOM 5 H5 IMI 1 3.315 -0.760 1.592 ATOM 6 C6 IMI 1 1.767 -1.114 0.071 ATOM 7 H7 IMI 1 1.658 -1.859 -0.707 ATOM 8 C8 IMI 1 0.602 -1.183 1.075 ATOM 9 H9 IMI 1 0.004 -2.078 0.925 ATOM 10 H10 IMI 1 0.928 -1.192 2.113 ATOM 11 C11 IMI 1 -0.149 0.095 0.730 ATOM 12 C12 IMI 1 0.540 0.903 -0.079 ATOM 13 C13 IMI 1 0.126 2.286 -0.641 ATOM 14 O14 IMI 1 -0.995 2.280 -1.159 ATOM 15 O15 IMI 1 0.957 3.159 -0.497 ATOM 16 C16 IMI 1 4.415 -1.683 0.010 ATOM 17 H17 IMI 1 4.390 -2.659 0.482 ATOM 18 C18 IMI 1 4.456 -1.870 -1.504 ATOM 19 H19 IMI 1 4.486 -0.914 -2.018 ATOM 20 H20 IMI 1 5.352 -2.421 -1.768 ATOM 21 H21 IMI 1 3.597 -2.424 -1.868 ATOM 22 O22 IMI 1 5.596 -1.076 0.467 ATOM 23 H23 IMI 1 5.597 -0.163 0.202 ATOM 24 S24 IMI 1 -1.629 0.596 1.545 ATOM 25 C25 IMI 1 -2.819 0.219 0.226 ATOM 26 H26 IMI 1 -2.563 -0.746 -0.196 ATOM 27 H27 IMI 1 -2.695 0.978 -0.536 ATOM 28 C28 IMI 1 -4.235 0.156 0.770 ATOM 29 H29 IMI 1 -4.323 -0.555 1.581 ATOM 30 H30 IMI 1 -4.586 1.118 1.115 ATOM 31 N31 IMI 1 -5.151 -0.293 -0.308 ATOM 32 H32 IMI 1 -5.159 0.281 -1.130 ATOM 33 C33 IMI 1 -5.827 -1.384 -0.302 ATOM 34 H34 IMI 1 -5.778 -1.997 0.578 ATOM 35 N35 IMI 1 -6.584 -1.819 -1.286 ATOM 36 H36 IMI 1 -7.071 -2.683 -1.202 ATOM 37 H37 IMI 1 -6.676 -1.325 -2.149

Bond, angle and torsion parameters added to build the MM model of imipenem. Some atom labels are shown in

the Scheme.

N

O

O

O

S

NH

NH

2

H

O

H

CI OI

NI

CT _CT



+

BOND

CI-OI 570.0 1.180

CI-CT 317.0 1.529

CI-NI 424.0 1.400

CT-NI 367.0 1.474

CM-NI 448.0 1.415

CM-S 227.0 1.763

CA-HP 367.0 1.080

ANGLE

CT-CI-OI 80.0 133.09

NI-CI-OI 80.0 134.32

NI-CI-CT 70.0 92.49

CI-NI-CM 70.0 128.78

CI-CT-HC 50.0 109.50

CI-CT-CT 63.0 111.10

NI-CM-C 80.0 122.13

NI-CM-CM 80.0 109.16

CI-NI-CT 80.0 93.02

ANGLE

CT-NI-CM 80.0 109.89

HP-CT-NI 50.0 109.50

CT-CT-NI 80.0 111.20

CM-S -CT 62.0 98.92

CT-CM-S 50.0 123.22

CM-CM-S 50.0 122.80

CM-C -O2 70.0 114.00

CT-CT-CM 80.0 100.79

DIHEDRAL

X -CI-NI-X 4 8.70 180.0 2.

X -CI-CT-X 4 0.00 0.0 2.

X -CT-NI-X 9 1.40 0.0 3.

X -CM-NI-X 4 7.40 180.0 2.

X -CM-S -X 3 1.00 0.0 3.

IMPROPER

New PM3 Zn and S parameters used in this study.

Atom Type ParameterName MNDO AM1 PM3 Zn Optimized OptimizedZn and S

Zinc Uss -20.839716 -21.040008 -18.532198 -16.974636 -17.669204 Upp -19.625224 -17.655574 -11.047409 -9.960559 -14.374732

s 2.047359 1.954299 1.819989 1.545214 1.516640

p 1.460946 1.372365 1.506922 1.484187 1.484187 AM 0.433664 0.433664 0.355649 0.270080 0.324814 AD 0.237591 0.231742 0.237569 0.225671 0.227947 AQ 0.273886 0.262117 0.266107 0.149239 0.140737

1 1.303783 1.358111 1.500576 1.712111 1.730663

2 1.452018 1.545741 1.407717 1.429281 1.429281

s -1.000000 -1.997429 -0.715578 -0.707312 -0.585816

p -2.000000 -4.758119 -6.351864 -4.407890 -4.333209 Gss 11.800000 11.800000 9.677196 7.348866 8.838188 Gpp 11.182018 13.300000 4.980174 5.546360 6.111817 Gsp 13.300000 11.182018 7.736204 10.011017 10.106278 Gpp' 12.930520 12.930520 4.669656 5.512569 6.085592 Hsp 0.484606 0.484606 0.600413 0.647232 0.672735

 1.506457 1.484563 1.350126 1.360252 1.365406 A1 0.000000 0.000000 -0.111234 -0.261469 -0.196261 A2 0.000000 0.000000 -0.132370 -0.144441 -0.110467 B1 0.000000 0.000000 6.001478 4.971166 3.647506 B2 0.000000 0.000000 1.995839 0.906124 1.336146 C1 0.000000 0.000000 1.516032 1.777252 1.771261 C2 0.000000 0.000000 2.519642 2.130155 2.451991 Atomic

Electronic

Energy -29.879432 -30.280016 -27.387200 -26.600406 -26.500219 Atomic

Heat Of

Formation 31.17 31.17 31.17 31.17 31.17

Sulfur Uss -72.242281 -56.694056 -49.895371 -49.895371 -51.416331

Upp -56.973207 -48.717049 -44.392583 -44.392583 -42.679855

s 2.312962 2.366515 1.891185 1.891185 1.663996

p 2.009146 1.667263 1.658972 1.658972 1.704563 AM 0.473355 0.433162 0.329462 0.329462 0.311718 AD 0.554450 0.590712 0.667912 0.667912 0.674218 AQ 0.558524 0.645494 0.613747 0.613747 0.565987

1 0.918994 0.900427 1.121431 1.121431 1.199148

2 0.832851 1.003633 1.008649 1.008649 0.981671

s -10.761670 -3.920566 -8.827465 -8.827465 -6.747934

p -10.108433 -7.905278 -8.091415 -8.091415 -8.251692 Gss 12.880000 11.786329 8.964667 8.964667 8.481847 Gpp 9.900000 10.039308 9.968164 9.968164 9.275413 Gsp 11.260000 8.663127 6.785936 6.785936 6.965764 Gpp' 8.830000 7.781688 7.970247 7.970247 7.743045 Hsp 2.260000 2.532137 4.041836 4.041836 4.357439

A3 0.000000 0.012334 0.000000 0.000000 0.000000 B1 0.000000 4.593691 6.000669 6.000669 5.491901 B2 0.000000 5.865731 6.001845 6.001845 10.989282 B3 0.000000 13.557336 0.000000 0.000000 0.000000 C1 0.000000 0.770665 0.962123 0.962123 0.964941 C2 0.000000 1.503313 1.579944 1.579944 1.740588 C3 0.000000 2.009173 0.000000 0.000000 0.000000 Atomic

Electronic

Energy -226.012390 -191.732193 -183.453740 -183.453740 -181.081790 Atomic

Heat of