Docking of glycopeptides /Cleavage of Thr-GalNAc bond

HADDOCK
1

Dear Prof. Bonvin, I tried to dock a glyco-peptide to an antibody using HADDOCK 2.4-web. As a result, the Thr-GalNAc linkage, which is the linkage between the sugar chain and the peptide, was cleaved.The glycan structure is Sia-Gal-GalNAc attached to Thr residue of the ligand peptide. Please let me know if there is a way to avoid this.The pdb of the ligands used are shown below.

REMARK BIOVIA PDB file
REMARK Created: 2021-12-09T14:54:59Z
ATOM 1 N ALA A 1 7.273 -0.781 1.149 1.00 20.00 N1+
ATOM 2 CA ALA A 1 7.162 -0.314 -0.225 1.00 20.00 C
ATOM 3 C ALA A 1 7.351 1.200 -0.359 1.00 20.00 C
ATOM 4 O ALA A 1 7.560 1.818 0.627 1.00 20.00 O
ATOM 5 CB ALA A 1 5.746 -0.689 -0.719 1.00 20.00 C
ATOM 6 HA ALA A 1 7.904 -0.824 -0.840 1.00 20.00 H
ATOM 7 HB1 ALA A 1 5.619 -0.356 -1.749 1.00 20.00 H
ATOM 8 HB2 ALA A 1 5.000 -0.206 -0.088 1.00 20.00 H
ATOM 9 HB3 ALA A 1 5.618 -1.770 -0.669 1.00 20.00 H
ATOM 10 HT1 ALA A 1 7.133 -1.841 1.178 1.00 20.00 H
ATOM 11 HT2 ALA A 1 6.525 -0.306 1.749 1.00 20.00 H
ATOM 12 HT3 ALA A 1 8.243 -0.540 1.531 1.00 20.00 H
ATOM 13 N HIS A 2 7.283 1.804 -1.537 1.00 20.00 N
ATOM 14 CA HIS A 2 7.449 3.233 -1.764 1.00 20.00 C
ATOM 15 C HIS A 2 7.315 3.623 -3.238 1.00 20.00 C
ATOM 16 O HIS A 2 7.098 2.762 -4.018 1.00 20.00 O
ATOM 17 CB HIS A 2 8.848 3.846 -1.419 1.00 20.00 C
ATOM 18 CG HIS A 2 9.238 3.841 0.032 1.00 20.00 C
ATOM 19 ND1 HIS A 2 10.301 4.482 0.502 1.00 20.00 N
ATOM 20 CD2 HIS A 2 8.568 3.222 1.075 1.00 20.00 C
ATOM 21 CE1 HIS A 2 10.333 4.287 1.817 1.00 20.00 C
ATOM 22 NE2 HIS A 2 9.291 3.530 2.146 1.00 20.00 N
ATOM 23 HN HIS A 2 7.097 1.314 -2.469 1.00 20.00 H
ATOM 24 HA HIS A 2 6.688 3.765 -1.194 1.00 20.00 H
ATOM 25 HB1 HIS A 2 9.602 3.281 -1.967 1.00 20.00 H
ATOM 26 HB2 HIS A 2 8.849 4.881 -1.760 1.00 20.00 H
ATOM 27 HD1 HIS A 2 11.003 5.051 -0.072 1.00 20.00 H
ATOM 28 HD2 HIS A 2 7.660 2.621 1.027 1.00 20.00 H
ATOM 29 HE1 HIS A 2 11.082 4.679 2.504 1.00 20.00 H
ATOM 30 N GLY A 3 7.436 4.882 -3.635 1.00 20.00 N
ATOM 31 CA GLY A 3 7.324 5.349 -5.009 1.00 20.00 C
ATOM 32 C GLY A 3 7.514 6.863 -5.143 1.00 20.00 C
ATOM 33 O GLY A 3 7.723 7.480 -4.157 1.00 20.00 O
ATOM 34 HN GLY A 3 7.632 5.713 -2.990 1.00 20.00 H
ATOM 35 HA1 GLY A 3 8.085 4.849 -5.609 1.00 20.00 H
ATOM 36 HA2 GLY A 3 6.335 5.088 -5.385 1.00 20.00 H
ATOM 37 N VAL A 4 7.446 7.467 -6.320 1.00 20.00 N
ATOM 38 CA VAL A 4 7.612 8.895 -6.547 1.00 20.00 C
ATOM 39 C VAL A 4 7.477 9.286 -8.022 1.00 20.00 C
ATOM 40 O VAL A 4 7.260 8.424 -8.802 1.00 20.00 O
ATOM 41 CB VAL A 4 9.078 9.275 -6.117 1.00 20.00 C
ATOM 42 CG1 VAL A 4 9.354 10.784 -6.285 1.00 20.00 C
ATOM 43 CG2 VAL A 4 9.320 8.910 -4.648 1.00 20.00 C
ATOM 44 HN VAL A 4 7.259 6.976 -7.253 1.00 20.00 H
ATOM 45 HA VAL A 4 6.893 9.453 -5.948 1.00 20.00 H
ATOM 46 HB VAL A 4 9.781 8.719 -6.737 1.00 20.00 H
ATOM 47 1HG1 VAL A 4 10.376 11.003 -5.977 1.00 20.00 H
ATOM 48 2HG1 VAL A 4 8.659 11.352 -5.666 1.00 20.00 H
ATOM 49 3HG1 VAL A 4 9.221 11.064 -7.330 1.00 20.00 H
ATOM 50 1HG2 VAL A 4 10.338 9.180 -4.369 1.00 20.00 H
ATOM 51 2HG2 VAL A 4 9.178 7.838 -4.510 1.00 20.00 H
ATOM 52 3HG2 VAL A 4 8.615 9.453 -4.017 1.00 20.00 H
ATOM 53 N THR A 5 7.599 10.544 -8.419 1.00 20.00 N
ATOM 54 CA THR A 5 7.486 11.012 -9.793 1.00 20.00 C
ATOM 55 C THR A 5 7.677 12.525 -9.927 1.00 20.00 C
ATOM 56 O THR A 5 7.887 13.143 -8.941 1.00 20.00 O
ATOM 57 CB THR A 5 6.072 10.613 -10.225 1.00 20.00 C
ATOM 58 OG1 THR A 5 5.894 9.202 -10.064 1.00 20.00 O
ATOM 59 CG2 THR A 5 5.856 11.000 -11.699 1.00 20.00 C
ATOM 60 HN THR A 5 7.795 11.375 -7.774 1.00 20.00 H
ATOM 61 HA THR A 5 8.217 10.495 -10.415 1.00 20.00 H
ATOM 62 HB THR A 5 5.346 11.140 -9.605 1.00 20.00 H
ATOM 63 1HG2 THR A 5 4.850 10.717 -12.006 1.00 20.00 H
ATOM 64 2HG2 THR A 5 6.585 10.482 -12.321 1.00 20.00 H
ATOM 65 3HG2 THR A 5 5.981 12.077 -11.814 1.00 20.00 H
ATOM 66 N SER A 6 7.608 13.130 -11.104 1.00 20.00 N
ATOM 67 CA SER A 6 7.775 14.558 -11.331 1.00 20.00 C
ATOM 68 C SER A 6 7.639 14.948 -12.806 1.00 20.00 C
ATOM 69 O SER A 6 7.421 14.087 -13.585 1.00 20.00 O
ATOM 70 CB SER A 6 9.193 14.881 -10.806 1.00 20.00 C
ATOM 71 OG SER A 6 10.128 14.137 -11.571 1.00 20.00 O
ATOM 72 HN SER A 6 7.421 12.639 -12.036 1.00 20.00 H
ATOM 73 HA SER A 6 7.039 15.105 -10.743 1.00 20.00 H
ATOM 74 HB1 SER A 6 9.392 15.947 -10.914 1.00 20.00 H
ATOM 75 HB2 SER A 6 9.270 14.601 -9.756 1.00 20.00 H
ATOM 76 HG SER A 6 9.930 13.112 -11.467 1.00 20.00 H
ATOM 77 N ALA A 7 7.761 16.207 -13.202 1.00 20.00 N
ATOM 78 CA ALA A 7 7.648 16.674 -14.576 1.00 20.00 C
ATOM 79 C ALA A 7 7.839 18.188 -14.711 1.00 20.00 C
ATOM 80 O ALA A 7 8.051 18.805 -13.725 1.00 20.00 O
ATOM 81 CB ALA A 7 6.230 16.301 -15.068 1.00 20.00 C
ATOM 82 HN ALA A 7 7.959 17.037 -12.558 1.00 20.00 H
ATOM 83 HA ALA A 7 8.388 16.163 -15.192 1.00 20.00 H
ATOM 84 HB1 ALA A 7 6.103 16.635 -16.097 1.00 20.00 H
ATOM 85 HB2 ALA A 7 5.487 16.785 -14.435 1.00 20.00 H
ATOM 86 HB3 ALA A 7 6.101 15.220 -15.018 1.00 20.00 H
ATOM 87 N PRO A 8 7.771 18.792 -15.888 1.00 20.00 N
ATOM 88 CA PRO A 8 7.938 20.220 -16.115 1.00 20.00 C
ATOM 89 C PRO A 8 6.764 21.051 -15.589 1.00 20.00 C
ATOM 90 O PRO A 8 5.871 20.476 -15.071 1.00 20.00 O
ATOM 91 HA PRO A 8 8.858 20.554 -15.634 1.00 20.00 H
ATOM 92 CB PRO A 8 8.006 20.262 -17.656 1.00 20.00 C
ATOM 93 CG PRO A 8 6.856 19.334 -17.984 1.00 20.00 C
ATOM 94 CD PRO A 8 7.250 18.134 -17.071 1.00 20.00 C
ATOM 95 HB1 PRO A 8 7.840 21.268 -18.043 1.00 20.00 H
ATOM 96 HB2 PRO A 8 8.956 19.881 -18.032 1.00 20.00 H
ATOM 97 HG1 PRO A 8 5.893 19.762 -17.706 1.00 20.00 H
ATOM 98 HG2 PRO A 8 6.840 19.059 -19.039 1.00 20.00 H
ATOM 99 HD1 PRO A 8 6.381 17.522 -16.830 1.00 20.00 H
ATOM 100 HD2 PRO A 8 8.011 17.514 -17.543 1.00 20.00 H
ATOM 101 N ASP A 9 6.743 22.371 -15.708 1.00 20.00 N
ATOM 102 CA ASP A 9 5.675 23.244 -15.241 1.00 20.00 C
ATOM 103 C ASP A 9 5.945 24.724 -15.527 1.00 20.00 C
ATOM 104 O ASP A 9 6.995 25.014 -16.097 1.00 20.00 O
ATOM 105 CB ASP A 9 5.662 22.973 -13.667 1.00 20.00 C
ATOM 106 CG ASP A 9 4.643 23.783 -12.870 1.00 20.00 C
ATOM 107 OD1 ASP A 9 4.478 23.532 -11.665 1.00 20.00 O
ATOM 108 OD2 ASP A 9 3.927 24.828 -13.445 1.00 20.00 O
ATOM 109 OXT ASP A 9 5.097 25.540 -15.169 1.00 20.00 O
ATOM 110 HN ASP A 9 7.511 22.959 -16.164 1.00 20.00 H
ATOM 111 HA ASP A 9 4.725 22.943 -15.682 1.00 20.00 H
ATOM 112 HB1 ASP A 9 5.448 21.916 -13.510 1.00 20.00 H
ATOM 113 HB2 ASP A 9 6.653 23.206 -13.279 1.00 20.00 H
TER 114 ASP A 9
HETATM 115 C1 A2G B 10 6.894 8.471 -10.910 1.00 1.80 C
HETATM 116 H1 A2G B 10 7.079 9.088 -11.789 1.00 1.33 H
HETATM 117 C2 A2G B 10 6.482 7.042 -11.248 1.00 1.80 C
HETATM 118 H2 A2G B 10 6.934 6.645 -12.157 1.00 1.33 H
HETATM 119 N2 A2G B 10 5.085 7.251 -11.490 1.00 1.83 N
HETATM 120 H2N A2G B 10 4.426 7.138 -10.746 1.00 0.80 H
HETATM 121 C2N A2G B 10 4.552 7.392 -12.731 1.00 1.87 C
HETATM 122 CME A2G B 10 3.025 7.513 -12.661 1.00 1.80 C
HETATM 123 H3M A2G B 10 2.476 6.605 -12.904 1.00 1.33 H
HETATM 124 H2M A2G B 10 2.744 7.705 -11.625 1.00 1.33 H
HETATM 125 H1M A2G B 10 2.677 8.374 -13.232 1.00 1.33 H
HETATM 126 O2N A2G B 10 5.192 7.459 -13.741 1.00 1.55 O
HETATM 127 C3 A2G B 10 6.746 6.075 -10.100 1.00 1.80 C
HETATM 128 H3 A2G B 10 6.031 6.368 -9.330 1.00 1.33 H
HETATM 129 C4 A2G B 10 8.078 6.202 -9.381 1.00 1.80 C
HETATM 130 H4 A2G B 10 7.984 5.551 -8.511 1.00 1.33 H
HETATM 131 C5 A2G B 10 8.176 7.701 -8.945 1.00 1.80 C
HETATM 132 H5 A2G B 10 7.364 7.809 -8.226 1.00 1.33 H
HETATM 133 C6 A2G B 10 9.481 8.064 -8.294 1.00 1.80 C
HETATM 134 H62 A2G B 10 9.628 7.522 -7.360 1.00 1.33 H
HETATM 135 H61 A2G B 10 10.331 7.725 -8.886 1.00 1.33 H
HETATM 136 O6 A2G B 10 9.739 9.418 -8.028 1.00 1.55 O
HETATM 137 H6O A2G B 10 9.459 9.895 -8.797 1.00 0.76 H
HETATM 138 O5 A2G B 10 8.087 8.472 -10.092 1.00 1.60 O
HETATM 139 O4 A2G B 10 9.259 5.730 -10.011 1.00 1.55 O
HETATM 140 H4O A2G B 10 9.345 6.308 -10.758 1.00 0.76 H
HETATM 141 O3 A2G B 10 6.591 4.707 -10.545 1.00 1.60 O
HETATM 142 C1 GAL B 11 5.294 4.078 -10.592 1.00 1.80 C
HETATM 143 H1 GAL B 11 4.571 4.737 -11.074 1.00 1.33 H
HETATM 144 O5 GAL B 11 4.865 3.700 -9.251 1.00 1.60 O
HETATM 145 C5 GAL B 11 3.582 3.073 -9.201 1.00 1.80 C
HETATM 146 H5 GAL B 11 2.968 3.818 -9.705 1.00 1.33 H
HETATM 147 C6 GAL B 11 2.970 3.056 -7.770 1.00 1.80 C
HETATM 148 H62 GAL B 11 2.948 2.092 -7.261 1.00 1.33 H
HETATM 149 H61 GAL B 11 1.929 3.375 -7.788 1.00 1.33 H
HETATM 150 O6 GAL B 11 3.744 3.960 -7.007 1.00 1.55 O
HETATM 151 H6O GAL B 11 4.633 3.632 -6.995 1.00 0.76 H
HETATM 152 C4 GAL B 11 3.639 1.721 -9.834 1.00 1.80 C
HETATM 153 H4 GAL B 11 2.611 1.362 -9.851 1.00 1.33 H
HETATM 154 O4 GAL B 11 4.507 0.751 -9.252 1.00 1.55 O
HETATM 155 H4O GAL B 11 4.518 -0.004 -9.825 1.00 0.76 H
HETATM 156 C3 GAL B 11 3.996 1.908 -11.312 1.00 1.80 C
HETATM 157 H3 GAL B 11 3.288 2.496 -11.895 1.00 1.33 H
HETATM 158 C2 GAL B 11 5.311 2.748 -11.443 1.00 1.80 C
HETATM 159 H2 GAL B 11 6.100 2.181 -10.950 1.00 1.33 H
HETATM 160 O2 GAL B 11 5.870 3.016 -12.722 1.00 1.55 O
HETATM 161 H2O GAL B 11 5.992 2.188 -13.167 1.00 0.76 H
HETATM 162 O3 GAL B 11 4.185 0.688 -11.977 1.00 1.60 O
HETATM 163 C2 SIA B 12 3.019 -0.055 -12.155 1.00 1.80 C
HETATM 164 C1 SIA B 12 3.127 -1.225 -11.060 1.00 1.87 C
HETATM 165 O1A SIA B 12 2.142 -1.512 -10.413 1.00 1.66 O
HETATM 166 O1B SIA B 12 4.272 -1.728 -10.974 1.00 1.66 O1-
HETATM 167 C3 SIA B 12 3.255 -0.637 -13.592 1.00 1.80 C
HETATM 168 H3E SIA B 12 4.106 -1.316 -13.634 1.00 1.33 H
HETATM 169 H3A SIA B 12 3.623 0.276 -14.059 1.00 1.33 H
HETATM 170 C4 SIA B 12 1.984 -1.088 -14.241 1.00 1.80 C
HETATM 171 H4 SIA B 12 1.594 -1.893 -13.618 1.00 1.33 H
HETATM 172 C5 SIA B 12 0.978 0.036 -14.232 1.00 1.80 C
HETATM 173 H5 SIA B 12 1.376 0.757 -14.945 1.00 1.33 H
HETATM 174 C6 SIA B 12 0.635 0.421 -12.709 1.00 1.80 C
HETATM 175 H6 SIA B 12 0.237 -0.487 -12.256 1.00 1.33 H
HETATM 176 C7 SIA B 12 -0.330 1.548 -12.625 1.00 1.80 C
HETATM 177 H7 SIA B 12 -0.927 1.424 -13.528 1.00 1.33 H
HETATM 178 C8 SIA B 12 -1.405 1.389 -11.521 1.00 1.80 C
HETATM 179 H8 SIA B 12 -1.756 0.369 -11.668 1.00 1.33 H
HETATM 180 C9 SIA B 12 -0.829 1.361 -10.070 1.00 1.80 C
HETATM 181 H9S SIA B 12 -0.029 0.632 -10.196 1.00 1.33 H
HETATM 182 H9R SIA B 12 -0.429 2.318 -9.737 1.00 1.33 H
HETATM 183 O9 SIA B 12 -1.822 0.877 -9.160 1.00 1.55 O
HETATM 184 H9O SIA B 12 -2.622 1.268 -9.487 1.00 0.76 H
HETATM 185 O8 SIA B 12 -2.374 2.358 -11.700 1.00 1.55 O
HETATM 186 H8O SIA B 12 -1.982 3.207 -11.544 1.00 0.76 H
HETATM 187 O7 SIA B 12 0.241 2.884 -12.656 1.00 1.55 O
HETATM 188 H7O SIA B 12 0.743 3.045 -13.443 1.00 0.76 H
HETATM 189 O6 SIA B 12 1.790 0.816 -12.030 1.00 1.60 O
HETATM 190 N5 SIA B 12 -0.218 -0.543 -14.900 1.00 1.83 N
HETATM 191 H5N SIA B 12 -0.584 -1.447 -14.679 1.00 0.80 H
HETATM 192 C5N SIA B 12 -0.626 -0.119 -16.128 1.00 1.87 C
HETATM 193 CME SIA B 12 -1.843 -0.910 -16.698 1.00 1.80 C
HETATM 194 H3M SIA B 12 -2.323 -0.284 -17.451 1.00 1.33 H
HETATM 195 H2M SIA B 12 -2.524 -1.036 -15.857 1.00 1.33 H
HETATM 196 H1M SIA B 12 -1.505 -1.834 -17.167 1.00 1.33 H
HETATM 197 O5N SIA B 12 -0.094 0.826 -16.774 1.00 1.55 O
HETATM 198 O4 SIA B 12 2.325 -1.479 -15.538 1.00 1.55 O
HETATM 199 H4O SIA B 12 1.525 -1.859 -15.877 1.00 0.76 H
TER 200 SIA B 12
CONECT 58 115
CONECT 115 58 116 117 138
CONECT 116 115
CONECT 117 115 118 119 127
CONECT 118 117
CONECT 119 117 120 121
CONECT 120 119
CONECT 121 119 122 126
CONECT 122 121 123 124 125
CONECT 123 122
CONECT 124 122
CONECT 125 122
CONECT 126 121
CONECT 127 117 128 129 141
CONECT 128 127
CONECT 129 127 130 131 139
CONECT 130 129
CONECT 131 129 132 133 138
CONECT 132 131
CONECT 133 131 134 135 136
CONECT 134 133
CONECT 135 133
CONECT 136 133 137
CONECT 137 136
CONECT 138 115 131
CONECT 139 129 140
CONECT 140 139
CONECT 141 127 142
CONECT 142 141 143 144 158
CONECT 143 142
CONECT 144 142 145
CONECT 145 144 146 147 152
CONECT 146 145
CONECT 147 145 148 149 150
CONECT 148 147
CONECT 149 147
CONECT 150 147 151
CONECT 151 150
CONECT 152 145 153 154 156
CONECT 153 152
CONECT 154 152 155
CONECT 155 154
CONECT 156 152 157 158 162
CONECT 157 156
CONECT 158 142 156 159 160
CONECT 159 158
CONECT 160 158 161
CONECT 161 160
CONECT 162 156 163
CONECT 163 162 164 167 189
CONECT 164 163 165 166
CONECT 165 164
CONECT 166 164
CONECT 167 163 168 169 170
CONECT 168 167
CONECT 169 167
CONECT 170 167 171 172 198
CONECT 171 170
CONECT 172 170 173 174 190
CONECT 173 172
CONECT 174 172 175 176 189
CONECT 175 174
CONECT 176 174 177 178 187
CONECT 177 176
CONECT 178 176 179 180 185
CONECT 179 178
CONECT 180 178 181 182 183
CONECT 181 180
CONECT 182 180
CONECT 183 180 184
CONECT 184 183
CONECT 185 178 186
CONECT 186 185
CONECT 187 176 188
CONECT 188 187
CONECT 189 163 174
CONECT 190 172 191 192
CONECT 191 190
CONECT 192 190 193 197
CONECT 193 192 194 195 196
CONECT 194 193
CONECT 195 193
CONECT 196 193
CONECT 197 192
CONECT 198 170 199
CONECT 199 198
END

2

Dear Shiho

The server does not (yet) support O-glycans…

But we put your request on our feature enhancement list.

4

Thank you for your reply.

I am currently trying to build a glycopeptide by docking a peptide to a protein and then docking a glycan to the protein-peptide complex.

When I set a 1.5 Å constraint between Thr Cb and GalNAc C1 hydroxyl oxygen, I was able to get as close as 3.3 Å and used the builder software to attach them.
(This constraint was set because when a restriction was set between the Thr side chain oxygen and GalNAcC1, the glycan was located at a place where it was difficult to construct an α-linkage.)
Is there any problem with the above method?
(I am worried that it may be distorted a little when the glycan chain is linked to Thr.)

5

You will never get as close at 1.5A because of the van der Waals interactions that will prevent close distance.
There is nothing much you can do about this.

For CYS for example (the covalent docking tutorial), we created a special residue without the H and with reduced radius of the sulphur atom to allow for closer distances.

6

Thank you for your reply.

I tried to process THR and GalNAc as well to make CYS into CYC, but THR and GalNAc do not support special residues without hydrogen, so I will try to dock and bind with distance restrictions.