CFTRG85EpathogenicCOMPLETEPCD-CFTR-G85E

Cystic Fibrosis

Class II — TM2 helix disruption collapses TM1-TM2 packing, causes ERAD retention

UniProt P13569ClinVar #7107Precursor G85E
fpocket Druggability0.807
Chaperone Composite0.907
Pocket Affinity1.000
Drug-likeness (QED)0.869
Stage 2 — Transient Pocket

Cryptic Binding Site

0.807
fpocket Drug.
0.003
WT Baseline
484.0
Volume (ų)
~35 (TMD1 focus)
α-Spheres
15
Conformations
11.3 Å
Mut→Pocket Dist.
Pocket Type
ICL1-TM2 junction — VX-809 canonical site destroyed (drug=0.003), alternative allosteric pocket exposed
Pocket Center (Å)
(-5.5, 19.9, -22.1)
Pocket-Lining Residues
I70L73R74F77F78F81L195
Sequence Slice (±20 aa around pocket)
KLINALRRCFFWRFMFYE
3D Structure
Transient pocket conformation · drag to rotate
Loading structure

MT conformations 1-15 (detection_freq=1.00, persistent across all mutant ensemble frames)

Stage 3 — De Novo Chaperone

REFOLD-PC-CFTR-001

SMILES String
O=C(c1cc(F)ccc1F)N1CCN(Cc2ccccc2)CC1
1-benzyl-4-(2,4-difluorobenzoyl)piperazine
Physicochemical Properties
316
MW (Da)
2.92
logP
0.869
QED
1.7
SA
0
HBD
2
HBA
32
TPSA (Ų)
Drug-likeness Rules
✓ Lipinski Ro5
✓ Veber Oral
✓ PAINS-free
Predicted Binding Mode
primary aromatic
2,4-F-phenyl π-stack with F77/F78 (T-shaped, ~4.5 Å)
secondary aromatic
Benzyl ring contacts F81 (~4.5 Å)
hbond
Carbonyl C=O ← R74 guanidinium NH₂ (~2.7 Å)
hydrophobic n
Piperazine CH₂ contacts I70, L73 (CH-π, ~3.8 Å)
back wall
N-benzyl contacts L195 vdW (~4.0 Å)
Stage 2 Output

Eᴵʲ Pairwise Distance Matrix

Cα–Cα distances (Å) between pocket-lining residues in the selected transient conformation. Used as conditioning input for Stage 3 pharmacophore-guided SMILES generation.

Shape 7 × 7Source data/results/CFTR_G85E/E_ij_matrix.npy
I70L73R74F77F78F81L195
I70
0.0
5.0
6.0
10.2
10.2
13.4
14.0
L73
5.0
0.0
3.9
6.0
7.6
10.9
13.2
R74
6.0
3.9
0.0
5.5
4.9
9.3
13.4
F77
10.2
6.0
5.5
0.0
3.9
6.2
11.7
F78
10.2
7.6
4.9
3.9
0.0
5.0
11.8
F81
13.4
10.9
9.3
6.2
5.0
0.0
8.6
L195
14.0
13.2
13.4
11.7
11.8
8.6
0.0
0 Å
14 Å
Sequence

Full Protein Sequence

>P13569|CFTR_HUMAN|G85E mutant (1480 AA)

MQRSPLEKASVVSKLFFSWTRPILRKGYRQRLELSDIYQIPSVDSADNLSEKLEREWDRELASKKNPKLINALRRCFFWRFMFYEIFLYLGEVTKAVQPLLLGRIIASYDPDNKEERSIAIYLGIGLCLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLSSRVLDKISIGQLVSLLSNNLNKFDEGLALAHFVWIAPLQVALLMGLIWELLQASAFCGLGFLIVLALFQAGLGRMMMKYRDQRAGKISERLVITSEMIENIQSVKAYCWEEAMEKMIENLRQTELKLTRKAAYVRYFNSSAFFFSGFFVVFLSVLPYALIKGIILRKIFTTISFCIVLRMAVTRQFPWAVQTWYDSLGAINKIQDFLQKQEYKTLEYNLTTTEVVMENVTAFWEEGFGELFEKAKQNNNNRKTSNGDDSLFFSNFSLLGTPVLKDINFKIERGQLLAVAGSTGAGKTSLLMVIMGELEPSEGKIKHSGRISFCSQFSWIMPGTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIVLGEGGITLSGGQRARISLARAVYKDADLYLLDSPFGYLDVLTEKEIFESCVCKLMANKTRILVTSKMEHLKKADKILILHEGSSYFYGTFSELQNLQPDFSSKLMGCDSFDQFSAERRNSILTETLHRFSLEGDAPVSWTETKKQSFKQTGEFGEKRKNSILNPINSIRKFSIVQKTPLQMNGIEEDSDEPLERRLSLVPDSEQGEAILPRISVISTGPTLQARRRQSVLNLMTHSVNQGQNIHRKTTASTRKVSLAPQANLTELDIYSRRLSQETGLEISEEINEEDLKECFFDDMESIPAVTTWNTYLRYITVHKSLIFVLIWCLVIFLAEVAASLVVLWLLGNTPLQDKGNSTHSRNNSYAVIITSTSSYYVFYIYVGVADTLLAMGFFRGLPLVHTLITVSKILHHKMLHSVLQAPMSTLNTLKAGGILNRFSKDIAILDDLLPLTIFDFIQLLLIVIGAIAVVAVLQPYIFVATVPVIVAFIMLRAYFLQTSQQLKQLESEGRSPIFTHLVTSLKGLWTLRAFGRQPYFETLFHKALNLHTANWFLYLSTLRWFQMRIEMIFVIFFIAVTFISILTTGEGEGRVGIILTLAMNIMSTLQWAVNSSIDVDSLMRSVSRVFKFIDMPTEGKPTKSTKPYKNGQLSKVMIIENSHVKKDDIWPSGGQMTVKDLTAKYTEGGNAILENISFSISPGQRVGLLGRTGSGKSTLLSAFLRLLNTEGEIQIDGVSWDSITLQQWRKAFGVIPQKVFIFSGTFRKNLDPYEQWSDQEIWKVADEVGLRSVIEQFPGKLDFVLVDGGCVLSHGHKQLMCLARSVLSKAKILLLDEPSAHLDPVTYQIIRRTLKQAFADCTVILCEHRIEAMLECQQFLVIEENKVRQYDSIQKLLNERSLFRQAISPSDRVKLFPHRNSSKCKSKPQIAALKEETEEEVQDTRL
Pocket-lining residues: ILRFFFL
Data Assets

Downloadable Files

E_ij Matrix (.npy)
data/results/CFTR_G85E/E_ij_matrix.npy
E_ij Matrix (.csv)
data/results/CFTR_G85E/E_ij_matrix.csv
Transient Conformation (.pdb)
data/results/CFTR_G85E/conformations/mt_01.pdb
Pocket Summary (.json)
data/results/CFTR_G85E/pocket_summary.json
Stage 3 Candidates (.json)
data/results/CFTR_G85E/stage3_chaperone_candidates.json
← Back to Database
REFOLD · S.Y.A.L.I.S Labs · Aaryan Senthilvanan