# GLP1R / GIPR ligand matrix, run 2 (2026-08-20).
#
# Pocket distance is 4A, not the 8A run 1 used. That is the single change, and it is
# the one the pose-optimisation series measured: with the GLP1R V6G pocket's own 62
# residues held fixed and nothing altered but the distance, orforglipron's pose against
# 7E14 went from 9.51A to 2.56A -- from the wrong binding mode to a reproduction of the
# crystal one. Contact counts are left exactly as run 1 had them: at a fixed 4A the
# series did not order by contact count (13 -> 3.70A, 25 -> 8.96A, 38 -> 2.04A,
# 62 -> 2.56A), so there is no evidence for tuning the residue lists and one sample
# per condition is too thin to justify it.

Settings:
Output folder: ./boltz_yamls
Predict affinity: yes
Pocket distance: 4
Targets per invocation: 4

Protein: GLP1R
Sequence: MAGAPGPLRLALLLLGMVGRAGPRPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNVSCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKWMYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQWIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLIFVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIKLFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERWRLEHLHIQRDSSMKPLKCPTSSLSSGATAGSSMYTATCQASCS
Partners: GNAS, GNB1, GNG2
# 5VEW, not 7rg9. Both are called apo, but 7rg9 is apo *and Gs-coupled* -- the
# active state without an agonist -- so comparing an agonist-bound active
# prediction against it measures active against active and TM6 barely moves
# (2.56A, 7.3 deg, measured). 5VEW is GLP-1R with the negative allosteric
# modulator PF-06372222, no G protein: a genuine inactive state, which is what
# the class B TM6 activation swing is defined against.
Apo structure: reference/5vew.cif
# 5VEW has two copies of the receptor in the asymmetric unit, and the T4-lysozyme
# fusion dilutes both to the same 0.6 identity against the family sequence, so the
# chain resolver cannot choose between them and refuses rather than guessing.
Apo chain: A
Pocket contact: GLP1R residue 154 as 41Y
Pocket contact: GLP1R residue 187 as 41Y
Pocket contact: GLP1R residue 321 as 41Y
Pocket contact: GLP1R residue 324 as 41Y
Pocket contact: GLP1R residue 325 as 41Y
Pocket contact: GLP1R residue 328 as 41Y
Pocket contact: GLP1R residue 350 as 41Y
Pocket contact: GLP1R residue 351 as 41Y
Pocket contact: GLP1R residue 353 as 41Y
Pocket contact: GLP1R residue 354 as 41Y
Pocket contact: GLP1R residue 355 as 41Y
Pocket contact: GLP1R residue 356 as 41Y
Pocket contact: GLP1R residue 357 as 41Y
Pocket contact: GLP1R residue 358 as 41Y
Pocket contact: GLP1R residue 359 as 41Y
Pocket contact: GLP1R residue 361 as 41Y
Pocket contact: GLP1R residue 362 as 41Y
Pocket contact: GLP1R residue 363 as 41Y
Pocket contact: GLP1R residue 364 as 41Y
Pocket contact: GLP1R residue 365 as 41Y
Pocket contact: GLP1R residue 366 as 41Y
Pocket contact: GLP1R residue 367 as 41Y
Pocket contact: GLP1R residue 386 as 41Y
Pocket contact: GLP1R residue 387 as 41Y
Pocket contact: GLP1R residue 388 as 41Y
Pocket contact: GLP1R residue 389 as 41Y
Pocket contact: GLP1R residue 390 as 41Y
Pocket contact: GLP1R residue 391 as 41Y
Pocket contact: GLP1R residue 392 as 41Y
Pocket contact: GLP1R residue 393 as 41Y
Pocket contact: GLP1R residue 394 as 41Y
Pocket contact: GLP1R residue 395 as 41Y
Pocket contact: GLP1R residue 396 as 41Y
Pocket contact: GLP1R residue 397 as 41Y
Pocket contact: GLP1R residue 398 as 41Y
Pocket contact: GLP1R residue 400 as 41Y
Pocket contact: GLP1R residue 401 as 41Y
Pocket contact: GLP1R residue 29 as V6G
Pocket contact: GLP1R residue 30 as V6G
Pocket contact: GLP1R residue 31 as V6G
Pocket contact: GLP1R residue 32 as V6G
Pocket contact: GLP1R residue 33 as V6G
Pocket contact: GLP1R residue 34 as V6G
Pocket contact: GLP1R residue 136 as V6G
Pocket contact: GLP1R residue 137 as V6G
Pocket contact: GLP1R residue 138 as V6G
Pocket contact: GLP1R residue 139 as V6G
Pocket contact: GLP1R residue 140 as V6G
Pocket contact: GLP1R residue 141 as V6G
Pocket contact: GLP1R residue 142 as V6G
Pocket contact: GLP1R residue 143 as V6G
Pocket contact: GLP1R residue 144 as V6G
Pocket contact: GLP1R residue 145 as V6G
Pocket contact: GLP1R residue 146 as V6G
Pocket contact: GLP1R residue 147 as V6G
Pocket contact: GLP1R residue 148 as V6G
Pocket contact: GLP1R residue 149 as V6G
Pocket contact: GLP1R residue 193 as V6G
Pocket contact: GLP1R residue 194 as V6G
Pocket contact: GLP1R residue 195 as V6G
Pocket contact: GLP1R residue 196 as V6G
Pocket contact: GLP1R residue 197 as V6G
Pocket contact: GLP1R residue 198 as V6G
Pocket contact: GLP1R residue 199 as V6G
Pocket contact: GLP1R residue 200 as V6G
Pocket contact: GLP1R residue 201 as V6G
Pocket contact: GLP1R residue 202 as V6G
Pocket contact: GLP1R residue 203 as V6G
Pocket contact: GLP1R residue 204 as V6G
Pocket contact: GLP1R residue 205 as V6G
Pocket contact: GLP1R residue 206 as V6G
Pocket contact: GLP1R residue 217 as V6G
Pocket contact: GLP1R residue 220 as V6G
Pocket contact: GLP1R residue 221 as V6G
Pocket contact: GLP1R residue 224 as V6G
Pocket contact: GLP1R residue 225 as V6G
Pocket contact: GLP1R residue 226 as V6G
Pocket contact: GLP1R residue 227 as V6G
Pocket contact: GLP1R residue 228 as V6G
Pocket contact: GLP1R residue 229 as V6G
Pocket contact: GLP1R residue 230 as V6G
Pocket contact: GLP1R residue 231 as V6G
Pocket contact: GLP1R residue 232 as V6G
Pocket contact: GLP1R residue 233 as V6G
Pocket contact: GLP1R residue 234 as V6G
Pocket contact: GLP1R residue 284 as V6G
Pocket contact: GLP1R residue 295 as V6G
Pocket contact: GLP1R residue 296 as V6G
Pocket contact: GLP1R residue 297 as V6G
Pocket contact: GLP1R residue 298 as V6G
Pocket contact: GLP1R residue 299 as V6G
Pocket contact: GLP1R residue 300 as V6G
Pocket contact: GLP1R residue 306 as V6G
Pocket contact: GLP1R residue 380 as V6G
Pocket contact: GLP1R residue 384 as V6G
Pocket contact: GLP1R residue 385 as V6G
Pocket contact: GLP1R residue 387 as V6G
Pocket contact: GLP1R residue 388 as V6G
Pocket contact: GLP1R residue 389 as V6G

Protein: GIPR
Sequence: MTTSPILQLLLRLSLCGLLLQRAETGSKGQTAGELYQRWERYRRECQETLAAAEPPSGLACNGSFDMYVCWDYAAPNATARASCPWYLPWHHHVAAGFVLRQCGSDGQWGLWRDHTQCENPEKNEAFLDQRLILERLQVMYTVGYSLSLATLLLALLILSLFRRLHCTRNYIHINLFTSFMLRAAAILSRDRLLPRPGPYLGDQALALWNQALAACRTAQIVTQYCVGANYTWLLVEGVYLHSLLVLVGGSEEGHFRYYLLLGWGAPALFVIPWVIVRYLYENTQCWERNEVKAIWWIIRTPILMTILINFLIFIRILGILLSKLRTRQMRCRDYRLRLARSTLTLVPLLGVHEVVFAPVTEEQARGALRFAKLGFEIFLSSFQGFLVSVLYCFINKEVQSEIRRGWHHCRLRRSLGEEQRQLPERAFRALPSGSGPGEVPTSRGLSSGTLPGPGNEASRELESYC
Partners: GNAS, GNB1, GNG2
Apo structure: reference/8wa3.cif
Pocket source: 41Y from 7RBT
Pocket contact: GIPR residue 147 as 41Y
Pocket contact: GIPR residue 180 as 41Y
Pocket contact: GIPR residue 311 as 41Y
Pocket contact: GIPR residue 314 as 41Y
Pocket contact: GIPR residue 315 as 41Y
Pocket contact: GIPR residue 318 as 41Y
Pocket contact: GIPR residue 340 as 41Y
Pocket contact: GIPR residue 341 as 41Y
Pocket contact: GIPR residue 343 as 41Y
Pocket contact: GIPR residue 344 as 41Y
Pocket contact: GIPR residue 345 as 41Y
Pocket contact: GIPR residue 346 as 41Y
Pocket contact: GIPR residue 347 as 41Y
Pocket contact: GIPR residue 348 as 41Y
Pocket contact: GIPR residue 349 as 41Y
Pocket contact: GIPR residue 351 as 41Y
Pocket contact: GIPR residue 352 as 41Y
Pocket contact: GIPR residue 353 as 41Y
Pocket contact: GIPR residue 354 as 41Y
Pocket contact: GIPR residue 355 as 41Y
Pocket contact: GIPR residue 356 as 41Y
Pocket contact: GIPR residue 357 as 41Y
Pocket contact: GIPR residue 376 as 41Y
Pocket contact: GIPR residue 377 as 41Y
Pocket contact: GIPR residue 378 as 41Y
Pocket contact: GIPR residue 379 as 41Y
Pocket contact: GIPR residue 380 as 41Y
Pocket contact: GIPR residue 381 as 41Y
Pocket contact: GIPR residue 382 as 41Y
Pocket contact: GIPR residue 383 as 41Y
Pocket contact: GIPR residue 384 as 41Y
Pocket contact: GIPR residue 385 as 41Y
Pocket contact: GIPR residue 386 as 41Y
Pocket contact: GIPR residue 387 as 41Y
Pocket contact: GIPR residue 388 as 41Y
Pocket contact: GIPR residue 390 as 41Y
Pocket contact: GIPR residue 391 as 41Y
Pocket contact: GIPR residue 3 as V6G
Pocket contact: GIPR residue 13 as V6G
Pocket contact: GIPR residue 14 as V6G
Pocket contact: GIPR residue 20 as V6G
Pocket contact: GIPR residue 23 as V6G
Pocket contact: GIPR residue 24 as V6G
Pocket contact: GIPR residue 130 as V6G
Pocket contact: GIPR residue 131 as V6G
Pocket contact: GIPR residue 132 as V6G
Pocket contact: GIPR residue 133 as V6G
Pocket contact: GIPR residue 134 as V6G
Pocket contact: GIPR residue 135 as V6G
Pocket contact: GIPR residue 136 as V6G
Pocket contact: GIPR residue 137 as V6G
Pocket contact: GIPR residue 138 as V6G
Pocket contact: GIPR residue 139 as V6G
Pocket contact: GIPR residue 140 as V6G
Pocket contact: GIPR residue 141 as V6G
Pocket contact: GIPR residue 142 as V6G
Pocket contact: GIPR residue 186 as V6G
Pocket contact: GIPR residue 187 as V6G
Pocket contact: GIPR residue 188 as V6G
Pocket contact: GIPR residue 189 as V6G
Pocket contact: GIPR residue 190 as V6G
Pocket contact: GIPR residue 191 as V6G
Pocket contact: GIPR residue 192 as V6G
Pocket contact: GIPR residue 193 as V6G
Pocket contact: GIPR residue 194 as V6G
Pocket contact: GIPR residue 195 as V6G
Pocket contact: GIPR residue 196 as V6G
Pocket contact: GIPR residue 197 as V6G
Pocket contact: GIPR residue 207 as V6G
Pocket contact: GIPR residue 210 as V6G
Pocket contact: GIPR residue 211 as V6G
Pocket contact: GIPR residue 214 as V6G
Pocket contact: GIPR residue 215 as V6G
Pocket contact: GIPR residue 216 as V6G
Pocket contact: GIPR residue 217 as V6G
Pocket contact: GIPR residue 218 as V6G
Pocket contact: GIPR residue 219 as V6G
Pocket contact: GIPR residue 220 as V6G
Pocket contact: GIPR residue 221 as V6G
Pocket contact: GIPR residue 222 as V6G
Pocket contact: GIPR residue 223 as V6G
Pocket contact: GIPR residue 224 as V6G
Pocket contact: GIPR residue 274 as V6G
Pocket contact: GIPR residue 285 as V6G
Pocket contact: GIPR residue 286 as V6G
Pocket contact: GIPR residue 287 as V6G
Pocket contact: GIPR residue 288 as V6G
Pocket contact: GIPR residue 289 as V6G
Pocket contact: GIPR residue 290 as V6G
Pocket contact: GIPR residue 296 as V6G
Pocket contact: GIPR residue 370 as V6G
Pocket contact: GIPR residue 374 as V6G
Pocket contact: GIPR residue 375 as V6G
Pocket contact: GIPR residue 377 as V6G
Pocket contact: GIPR residue 378 as V6G
Pocket contact: GIPR residue 379 as V6G

Protein: GLPAP
Sequence: MAGAPGPLRLALLLLGMVGRAGPRPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNVSCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKWMYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQWIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLIFVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIKLFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERWRLEHLHIQRDSSMKPLKCPTSSLSSGATAGSSMYTATCQASCS
Partners: GNAS, GNB1, GNG2
Ligands: none

Protein: GIPAP
Sequence: MTTSPILQLLLRLSLCGLLLQRAETGSKGQTAGELYQRWERYRRECQETLAAAEPPSGLACNGSFDMYVCWDYAAPNATARASCPWYLPWHHHVAAGFVLRQCGSDGQWGLWRDHTQCENPEKNEAFLDQRLILERLQVMYTVGYSLSLATLLLALLILSLFRRLHCTRNYIHINLFTSFMLRAAAILSRDRLLPRPGPYLGDQALALWNQALAACRTAQIVTQYCVGANYTWLLVEGVYLHSLLVLVGGSEEGHFRYYLLLGWGAPALFVIPWVIVRYLYENTQCWERNEVKAIWWIIRTPILMTILINFLIFIRILGILLSKLRTRQMRCRDYRLRLARSTLTLVPLLGVHEVVFAPVTEEQARGALRFAKLGFEIFLSSFQGFLVSVLYCFINKEVQSEIRRGWHHCRLRRSLGEEQRQLPERAFRALPSGSGPGEVPTSRGLSSGTLPGPGNEASRELESYC
Partners: GNAS, GNB1, GNG2
Ligands: none

Partner: GNAS
Sequence: MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQMRILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL

Partner: GNB1
Sequence: MSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Partner: GNG2
Sequence: MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPFREKKFFCAIL

Ligand: ORFO
SMILES: C[C@H]1C[C@]1(C2=NOC(=O)N2)N3C4=C(C=C(C=C4)[C@H]5CCOC(C5)(C)C)C=C3C(=O)N6CCC7=NN(C(=C7[C@@H]6C)N8C=CN(C8=O)C9=C(C1=C(C=C9)N(N=C1)C)F)C1=CC(=C(C(=C1)C)F)C
Class: control

Ligand: LSN1
SMILES: COc1ccc2c(c1-c1cc(F)c(O)c(NCC(C)C)c1)CCN([C@@H](C)c1ccc(C(C)C)cc1)[C@@H]2C
Class: control

Ligand: LSN2
SMILES: COC[C@@H]1Cc2c(ccc(OC)c2-c2ccc(O)c(C)c2)CN1Cc1ccc(C(C)C)cc1O
Class: control