Supplementary Materials 2

Supplementary Materials 2

Single Active Site Mutation Causes Serious Resistance of HIV Reverse Transcriptase to Lamivudine: Insight from Molecular Dynamics Simulations

Suri Moonsamya,1, Soumendranath Bhakata,1 , Ross C. Walkerb and Mahmoud E. S. Solimana*

aSchool of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001,

South Africa

b San Diego Supercomputer Center & Department of Chemistry and Biochemistry, University of California, 9500 Gilman Drive, La Jolla, CA, 92093-0505, USA.

* Corresponding author: Mahmoud E.S. Soliman, email:

Telephone: +27 031 260 7413, Fax: +27 031 260 779

1 Authors contributed equally

Binding free energy results and PDB coordinates of the ionized phosphate group attached to the ligand

Figure S1. RMSD vs. time of wild and M184I variant of HIV-RT complexed with ionized from of lamivudine triphosphate. The RMSD datas were averaged over 4*5ns multiple MD run in each case

Figure S1. Potential Energy (kcal/mol) vs. time of wild and M184I variant of HIV-RT complexed with ionized from of lamivudine triphosphate. The Potential Energy datas were averaged over 4*5ns multiple MD run in each case

Table S1 Binding free energy for M184I. All the datas were averaged from a 4*5ns multiple MD run (validation of the results)

Complexes / ∆Gbind / ∆Eele / ∆EvdW / ∆Ggas / ∆Gsolv
Wild / -55.8380±0.1077 / -34.7539±0.1001 / -49.5484±0.1198 / -75.0867±0.2078 / 28.4643±0.1075
M184I / -40.4081±0.1086 / -23.5467±0.2087 / -38.9475±0.1909 / -59.5085±0.2975 / 22.0861±0.2070

PDB coordinates of the RT-Lamivudine complexes in the ionized form of phosphate group attached to ligand, mutant (a) and wild (b):

(a) PDB coordinates of lamivudine in complex with M184I mutant RT (ionized phosphate)

REMARK default_name

HELIX 1 1 GLU 28 LYS 43 1 16

HELIX 2 2 ARG 78 ARG 83 1 6

HELIX 3 3 PRO 97 GLY 99 1 3

HELIX 4 4 ALA 114 SER 117 1 4

HELIX 5 5 PHE 124 THR 128 1 5

HELIX 6 6 GLY 155 GLN 174 1 20

HELIX 7 7 ILE 195 ARG 211 1 17

HELIX 8 8 VAL 254 GLN 269 1 16

HELIX 9 9 LEU 279 LEU 283 1 5

HELIX 10 10 GLU 297 ILE 309 1 13

HELIX 11 11 ASP 364 TRP 383 1 20

HELIX 12 12 LYS 395 GLU 404 1 10

HELIX 13 13 ASN 474 GLN 487 1 14

HELIX 14 14 GLN 500 ALA 508 1 9

HELIX 15 15 GLU 516 ILE 526 1 11

HELIX 16 16 ASN 545 GLY 555 1 11

SHEET 1 1 1 ILE 47 LYS 49 0

SHEET 2 2 1 VAL 60 LYS 64 0

SHEET 3 3 1 TRP 71 VAL 75 0

SHEET 4 4 1 SER 105 LEU 109 0

SHEET 5 5 1 TYR 144 TYR 146 0

SHEET 6 6 1 VAL 179 TYR 183 0

SHEET 7 7 1 ASP 186 SER 191 0

SHEET 8 8 1 PHE 227 TRP 229 0

SHEET 9 9 1 TYR 232 LEU 234 0

SHEET 10 10 1 TRP 239 VAL 241 0

SHEET 11 11 1 ILE 326 GLY 333 0

SHEET 12 12 1 GLN 336 TYR 342 0

SHEET 13 13 1 ASN 348 TYR 354 0

SHEET 14 14 1 LYS 388 LEU 391 0

SHEET 15 15 1 TRP 414 PHE 416 0

SHEET 16 16 1 GLU 438 ALA 446 0

SHEET 17 17 1 GLY 453 THR 459 0

SHEET 18 18 1 GLN 464 LEU 469 0

SHEET 19 19 1 GLU 492 THR 497 0

SHEET 20 20 1 LYS 530 TRP 535 0

ATOM 1 N PRO 1 32.055 26.128 91.750 1.00 0.00 N

ATOM 2 H2 PRO 1 32.700 26.908 91.888 1.00 0.00 H

ATOM 3 H3 PRO 1 32.222 25.463 92.505 1.00 0.00 H

ATOM 4 CD PRO 1 30.646 26.579 91.730 1.00 0.00 C

ATOM 5 HD2 PRO 1 30.540 27.570 92.168 1.00 0.00 H

ATOM 6 HD3 PRO 1 30.031 25.871 92.291 1.00 0.00 H

ATOM 7 CG PRO 1 30.178 26.593 90.278 1.00 0.00 C

ATOM 8 HG2 PRO 1 30.474 27.528 89.794 1.00 0.00 H

ATOM 9 HG3 PRO 1 29.099 26.450 90.196 1.00 0.00 H

ATOM 10 CB PRO 1 30.960 25.415 89.696 1.00 0.00 C

ATOM 11 HB2 PRO 1 31.076 25.495 88.611 1.00 0.00 H

ATOM 12 HB3 PRO 1 30.458 24.480 89.950 1.00 0.00 H

ATOM 13 CA PRO 1 32.305 25.494 90.435 1.00 0.00 C

ATOM 14 HA PRO 1 32.689 24.483 90.582 1.00 0.00 H

ATOM 15 C PRO 1 33.352 26.281 89.635 1.00 0.00 C

ATOM 16 O PRO 1 33.297 27.509 89.613 1.00 0.00 O

ATOM 17 N ILE 2 34.292 25.565 89.006 1.00 0.00 N

ATOM 18 H ILE 2 34.241 24.558 89.065 1.00 0.00 H

ATOM 19 CA ILE 2 35.303 26.110 88.080 1.00 0.00 C

ATOM 20 HA ILE 2 34.947 27.076 87.715 1.00 0.00 H

ATOM 21 CB ILE 2 36.677 26.352 88.762 1.00 0.00 C

ATOM 22 HB ILE 2 37.093 25.381 89.042 1.00 0.00 H

ATOM 23 CG2 ILE 2 37.645 27.048 87.779 1.00 0.00 C

ATOM 24 HG21 ILE 2 37.300 28.063 87.576 1.00 0.00 H

ATOM 25 HG22 ILE 2 38.649 27.083 88.202 1.00 0.00 H

ATOM 26 HG23 ILE 2 37.717 26.528 86.828 1.00 0.00 H

ATOM 27 CG1 ILE 2 36.569 27.201 90.048 1.00 0.00 C

ATOM 28 HG12 ILE 2 36.297 28.225 89.790 1.00 0.00 H

ATOM 29 HG13 ILE 2 35.789 26.802 90.696 1.00 0.00 H

ATOM 30 CD1 ILE 2 37.855 27.202 90.881 1.00 0.00 C

ATOM 31 HD11 ILE 2 38.664 27.702 90.355 1.00 0.00 H

ATOM 32 HD12 ILE 2 37.667 27.730 91.809 1.00 0.00 H

ATOM 33 HD13 ILE 2 38.146 26.179 91.115 1.00 0.00 H

ATOM 34 C ILE 2 35.363 25.176 86.854 1.00 0.00 C

ATOM 35 O ILE 2 34.407 25.159 86.089 1.00 0.00 O

ATOM 36 N SER 3 36.412 24.359 86.701 1.00 0.00 N

ATOM 37 H SER 3 37.153 24.408 87.375 1.00 0.00 H

ATOM 38 CA SER 3 36.600 23.401 85.601 1.00 0.00 C

ATOM 39 HA SER 3 35.653 22.888 85.420 1.00 0.00 H

ATOM 40 CB SER 3 36.988 24.156 84.314 1.00 0.00 C

ATOM 41 HB2 SER 3 36.152 24.775 84.015 1.00 0.00 H

ATOM 42 HB3 SER 3 37.860 24.797 84.520 1.00 0.00 H

ATOM 43 OG SER 3 37.290 23.298 83.258 1.00 0.00 O

ATOM 44 HG SER 3 36.421 23.160 82.813 1.00 0.00 H

ATOM 45 C SER 3 37.700 22.377 85.937 1.00 0.00 C

ATOM 46 O SER 3 38.598 22.695 86.720 1.00 0.00 O

ATOM 47 N PRO 4 37.672 21.162 85.354 1.00 0.00 N

ATOM 48 CD PRO 4 36.527 20.560 84.673 1.00 0.00 C

ATOM 49 HD2 PRO 4 36.327 21.058 83.730 1.00 0.00 H

ATOM 50 HD3 PRO 4 35.645 20.599 85.312 1.00 0.00 H

ATOM 51 CG PRO 4 36.896 19.102 84.399 1.00 0.00 C

ATOM 52 HG2 PRO 4 37.285 18.998 83.386 1.00 0.00 H

ATOM 53 HG3 PRO 4 36.047 18.440 84.551 1.00 0.00 H

ATOM 54 CB PRO 4 38.009 18.830 85.409 1.00 0.00 C

ATOM 55 HB2 PRO 4 38.649 18.002 85.099 1.00 0.00 H

ATOM 56 HB3 PRO 4 37.572 18.626 86.389 1.00 0.00 H

ATOM 57 CA PRO 4 38.746 20.172 85.446 1.00 0.00 C

ATOM 58 HA PRO 4 39.264 20.267 86.400 1.00 0.00 H

ATOM 59 C PRO 4 39.806 20.285 84.327 1.00 0.00 C

ATOM 60 O PRO 4 40.628 19.378 84.196 1.00 0.00 O

ATOM 61 N ILE 5 39.798 21.337 83.494 1.00 0.00 N

ATOM 62 H ILE 5 39.098 22.058 83.615 1.00 0.00 H

ATOM 63 CA ILE 5 40.840 21.533 82.470 1.00 0.00 C

ATOM 64 HA ILE 5 40.936 20.580 81.949 1.00 0.00 H

ATOM 65 CB ILE 5 40.428 22.598 81.425 1.00 0.00 C

ATOM 66 HB ILE 5 39.424 22.339 81.093 1.00 0.00 H

ATOM 67 CG2 ILE 5 40.379 24.017 82.010 1.00 0.00 C

ATOM 68 HG21 ILE 5 41.385 24.363 82.245 1.00 0.00 H

ATOM 69 HG22 ILE 5 39.927 24.698 81.290 1.00 0.00 H

ATOM 70 HG23 ILE 5 39.785 24.027 82.918 1.00 0.00 H

ATOM 71 CG1 ILE 5 41.335 22.651 80.171 1.00 0.00 C

ATOM 72 HG12 ILE 5 40.933 23.394 79.482 1.00 0.00 H

ATOM 73 HG13 ILE 5 42.331 22.993 80.451 1.00 0.00 H

ATOM 74 CD1 ILE 5 41.476 21.331 79.397 1.00 0.00 C

ATOM 75 HD11 ILE 5 40.489 20.958 79.120 1.00 0.00 H

ATOM 76 HD12 ILE 5 42.060 21.502 78.488 1.00 0.00 H

ATOM 77 HD13 ILE 5 41.991 20.584 80.002 1.00 0.00 H

ATOM 78 C ILE 5 42.207 21.832 83.102 1.00 0.00 C

ATOM 79 O ILE 5 42.312 22.506 84.127 1.00 0.00 O

ATOM 80 N GLU 6 43.272 21.359 82.455 1.00 0.00 N

ATOM 81 H GLU 6 43.127 20.785 81.642 1.00 0.00 H

ATOM 82 CA GLU 6 44.649 21.668 82.839 1.00 0.00 C

ATOM 83 HA GLU 6 44.797 21.361 83.876 1.00 0.00 H

ATOM 84 CB GLU 6 45.635 20.887 81.959 1.00 0.00 C

ATOM 85 HB2 GLU 6 45.424 21.089 80.906 1.00 0.00 H

ATOM 86 HB3 GLU 6 46.645 21.234 82.184 1.00 0.00 H

ATOM 87 CG GLU 6 45.555 19.377 82.219 1.00 0.00 C

ATOM 88 HG2 GLU 6 45.771 19.190 83.275 1.00 0.00 H

ATOM 89 HG3 GLU 6 44.543 19.025 82.010 1.00 0.00 H

ATOM 90 CD GLU 6 46.554 18.593 81.364 1.00 0.00 C

ATOM 91 OE1 GLU 6 47.733 18.995 81.293 1.00 0.00 O

ATOM 92 OE2 GLU 6 46.192 17.515 80.837 1.00 0.00 O

ATOM 93 C GLU 6 44.944 23.173 82.748 1.00 0.00 C

ATOM 94 O GLU 6 44.655 23.821 81.737 1.00 0.00 O

ATOM 95 N THR 7 45.562 23.712 83.801 1.00 0.00 N

ATOM 96 H THR 7 45.829 23.118 84.571 1.00 0.00 H

ATOM 97 CA THR 7 46.057 25.089 83.852 1.00 0.00 C

ATOM 98 HA THR 7 45.238 25.767 83.609 1.00 0.00 H

ATOM 99 CB THR 7 46.584 25.435 85.257 1.00 0.00 C

ATOM 100 HB THR 7 47.089 26.401 85.221 1.00 0.00 H

ATOM 101 CG2 THR 7 45.466 25.493 86.293 1.00 0.00 C

ATOM 102 HG21 THR 7 45.004 24.512 86.404 1.00 0.00 H

ATOM 103 HG22 THR 7 45.871 25.809 87.253 1.00 0.00 H

ATOM 104 HG23 THR 7 44.715 26.206 85.970 1.00 0.00 H

ATOM 105 OG1 THR 7 47.474 24.445 85.722 1.00 0.00 O

ATOM 106 HG1 THR 7 48.056 24.837 86.379 1.00 0.00 H

ATOM 107 C THR 7 47.176 25.286 82.831 1.00 0.00 C

ATOM 108 O THR 7 48.101 24.476 82.746 1.00 0.00 O

ATOM 109 N VAL 8 47.133 26.380 82.066 1.00 0.00 N

ATOM 110 H VAL 8 46.375 27.033 82.186 1.00 0.00 H

ATOM 111 CA VAL 8 48.249 26.745 81.179 1.00 0.00 C

ATOM 112 HA VAL 8 48.626 25.828 80.730 1.00 0.00 H

ATOM 113 CB VAL 8 47.803 27.664 80.028 1.00 0.00 C

ATOM 114 HB VAL 8 47.424 28.599 80.442 1.00 0.00 H

ATOM 115 CG1 VAL 8 48.974 27.969 79.082 1.00 0.00 C

ATOM 116 HG11 VAL 8 49.408 27.042 78.711 1.00 0.00 H

ATOM 117 HG12 VAL 8 48.637 28.547 78.225 1.00 0.00 H

ATOM 118 HG13 VAL 8 49.738 28.548 79.604 1.00 0.00 H

ATOM 119 CG2 VAL 8 46.691 27.006 79.196 1.00 0.00 C

ATOM 120 HG21 VAL 8 45.803 26.850 79.809 1.00 0.00 H

ATOM 121 HG22 VAL 8 46.422 27.648 78.358 1.00 0.00 H

ATOM 122 HG23 VAL 8 47.035 26.045 78.814 1.00 0.00 H

ATOM 123 C VAL 8 49.356 27.392 82.026 1.00 0.00 C

ATOM 124 O VAL 8 49.041 28.326 82.769 1.00 0.00 O

ATOM 125 N PRO 9 50.619 26.930 81.943 1.00 0.00 N

ATOM 126 CD PRO 9 51.104 25.849 81.094 1.00 0.00 C

ATOM 127 HD2 PRO 9 50.805 25.984 80.057 1.00 0.00 H

ATOM 128 HD3 PRO 9 50.729 24.896 81.468 1.00 0.00 H

ATOM 129 CG PRO 9 52.626 25.882 81.202 1.00 0.00 C

ATOM 130 HG2 PRO 9 53.028 26.581 80.467 1.00 0.00 H

ATOM 131 HG3 PRO 9 53.060 24.891 81.070 1.00 0.00 H

ATOM 132 CB PRO 9 52.853 26.424 82.613 1.00 0.00 C

ATOM 133 HB2 PRO 9 53.829 26.901 82.710 1.00 0.00 H

ATOM 134 HB3 PRO 9 52.751 25.611 83.334 1.00 0.00 H

ATOM 135 CA PRO 9 51.701 27.417 82.796 1.00 0.00 C

ATOM 136 HA PRO 9 51.372 27.389 83.832 1.00 0.00 H

ATOM 137 C PRO 9 52.115 28.848 82.434 1.00 0.00 C

ATOM 138 O PRO 9 52.232 29.178 81.250 1.00 0.00 O

ATOM 139 N VAL 10 52.355 29.693 83.442 1.00 0.00 N

ATOM 140 H VAL 10 52.250 29.340 84.396 1.00 0.00 H

ATOM 141 CA VAL 10 52.603 31.137 83.260 1.00 0.00 C

ATOM 142 HA VAL 10 52.980 31.297 82.251 1.00 0.00 H

ATOM 143 CB VAL 10 51.277 31.913 83.398 1.00 0.00 C

ATOM 144 HB VAL 10 50.722 31.528 84.256 1.00 0.00 H

ATOM 145 CG1 VAL 10 51.442 33.423 83.599 1.00 0.00 C

ATOM 146 HG11 VAL 10 51.898 33.884 82.723 1.00 0.00 H

ATOM 147 HG12 VAL 10 50.463 33.843 83.797 1.00 0.00 H

ATOM 148 HG13 VAL 10 52.045 33.634 84.479 1.00 0.00 H

ATOM 149 CG2 VAL 10 50.434 31.724 82.129 1.00 0.00 C

ATOM 150 HG21 VAL 10 50.094 30.691 82.062 1.00 0.00 H

ATOM 151 HG22 VAL 10 49.560 32.363 82.146 1.00 0.00 H

ATOM 152 HG23 VAL 10 51.035 31.955 81.250 1.00 0.00 H

ATOM 153 C VAL 10 53.665 31.683 84.217 1.00 0.00 C

ATOM 154 O VAL 10 53.675 31.368 85.405 1.00 0.00 O

ATOM 155 N LYS 11 54.539 32.569 83.711 1.00 0.00 N

ATOM 156 H LYS 11 54.475 32.768 82.715 1.00 0.00 H

ATOM 157 CA LYS 11 55.626 33.203 84.481 1.00 0.00 C

ATOM 158 HA LYS 11 55.439 33.020 85.540 1.00 0.00 H

ATOM 159 CB LYS 11 56.967 32.518 84.126 1.00 0.00 C

ATOM 160 HB2 LYS 11 57.118 32.544 83.045 1.00 0.00 H

ATOM 161 HB3 LYS 11 57.785 33.062 84.601 1.00 0.00 H

ATOM 162 CG LYS 11 56.993 31.058 84.623 1.00 0.00 C

ATOM 163 HG2 LYS 11 56.772 31.059 85.692 1.00 0.00 H

ATOM 164 HG3 LYS 11 56.216 30.488 84.113 1.00 0.00 H

ATOM 165 CD LYS 11 58.333 30.338 84.405 1.00 0.00 C

ATOM 166 HD2 LYS 11 58.533 30.244 83.337 1.00 0.00 H

ATOM 167 HD3 LYS 11 59.131 30.914 84.876 1.00 0.00 H

ATOM 168 CE LYS 11 58.236 28.946 85.052 1.00 0.00 C

ATOM 169 HE2 LYS 11 57.856 29.078 86.070 1.00 0.00 H

ATOM 170 HE3 LYS 11 57.506 28.345 84.503 1.00 0.00 H

ATOM 171 NZ LYS 11 59.540 28.241 85.122 1.00 0.00 N

ATOM 172 HZ1 LYS 11 60.217 28.806 85.622 1.00 0.00 H

ATOM 173 HZ2 LYS 11 59.443 27.383 85.645 1.00 0.00 H

ATOM 174 HZ3 LYS 11 59.900 27.970 84.206 1.00 0.00 H

ATOM 175 C LYS 11 55.683 34.734 84.331 1.00 0.00 C

ATOM 176 O LYS 11 55.200 35.324 83.362 1.00 0.00 O

ATOM 177 N LEU 12 56.304 35.385 85.317 1.00 0.00 N

ATOM 178 H LEU 12 56.683 34.827 86.064 1.00 0.00 H

ATOM 179 CA LEU 12 56.763 36.777 85.222 1.00 0.00 C

ATOM 180 HA LEU 12 55.987 37.382 84.759 1.00 0.00 H

ATOM 181 CB LEU 12 57.048 37.339 86.632 1.00 0.00 C

ATOM 182 HB2 LEU 12 57.804 36.709 87.105 1.00 0.00 H

ATOM 183 HB3 LEU 12 57.479 38.337 86.534 1.00 0.00 H

ATOM 184 CG LEU 12 55.824 37.432 87.567 1.00 0.00 C