GBA1L444PpathogenicCOMPLETEPCD-GBA1-L444P

Gaucher Disease Type 1

ER retention / ERAD — misfolded β-glucocerebrosidase fails ER quality control

UniProt P04062ClinVar #4288Precursor L483P
fpocket Druggability0.926
Chaperone Composite0.956
Pocket Affinity0.998
Drug-likeness (QED)0.795
Stage 2 — Transient Pocket

Cryptic Binding Site

0.926
fpocket Drug.
0.183
WT Baseline
462.6
Volume (ų)
63
α-Spheres
25
Conformations
23.5 Å
Mut→Pocket Dist.
Pocket Type
TRANSIENT_MISFOLDING — absent in WT, exposes in L444P mutant ensemble
Pocket Center (Å)
(8.0, -4.0, 16.1)
Pocket-Lining Residues
A40R41P42C43D63S64F65R87M88E89L90
Sequence Slice (±20 aa around pocket)
ARPCIPKSFGYSSVVCVCNATYCDSFDPPTFPALGTFSRYESTRSGRRMELS
3D Structure
Transient pocket conformation · drag to rotate
Loading structure

MT conformation 10 (seed=110, ANM L444P ensemble)

Stage 3 — De Novo Chaperone

REFOLD-PC-GBA1-001

SMILES String
O=C(NCc1ccc(O)c(N2CCCCC2)c1)C1CCNCC1
4-piperidinyl-N-(4-hydroxy-3-piperidinylbenzyl)carboxamide analog
Physicochemical Properties
317
MW (Da)
2.00
logP
0.795
QED
2.7
SA
3
HBD
4
HBA
65
TPSA (Ų)
Drug-likeness Rules
✓ Lipinski Ro5
✓ Veber Oral
✓ PAINS-free
Predicted Binding Mode
primary hbond
Pip-NH → D24 carboxylate (salt bridge ~2.6 Å)
secondary hbond
Amide C=O ← R2 guanidinium (~2.8 Å)
phenol hbond
Phenol-OH → D24 Oδ (~2.5 Å)
aromatic stacking
Phenyl π-π with F26 (~4.5 Å T-shaped)
hydrophobic
Pip ring vdW with P3, A1, M49, L51
salt bridge
N-aryl-pip → E50 carboxylate (~3.0 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 11 × 11Source data/results/GBA_L444P/E_ij_matrix_MT10_pocket1.npy
A40R41P42C43D63S64F65R87M88E89L90
A40
0.0
3.8
6.5
9.7
7.1
5.1
4.4
11.5
10.7
9.9
10.0
R41
3.8
0.0
3.9
6.9
4.7
4.9
6.7
10.8
11.4
10.7
12.0
P42
6.5
3.9
0.0
3.8
5.0
6.8
8.2
8.0
9.5
8.7
11.0
C43
9.7
6.9
3.8
0.0
5.0
8.1
10.1
6.8
9.5
9.7
12.9
D63
7.1
4.7
5.0
5.0
0.0
3.8
7.1
9.2
10.4
11.3
13.4
S64
5.1
4.9
6.8
8.1
3.8
0.0
3.8
10.1
9.8
10.8
11.9
F65
4.4
6.7
8.2
10.1
7.1
3.8
0.0
10.0
8.3
8.9
9.0
R87
11.5
10.8
8.0
6.8
9.2
10.1
10.0
0.0
3.8
5.4
9.0
M88
10.7
11.4
9.5
9.5
10.4
9.8
8.3
3.8
0.0
3.9
6.3
E89
9.9
10.7
8.7
9.7
11.3
10.8
8.9
5.4
3.9
0.0
3.8
L90
10.0
12.0
11.0
12.9
13.4
11.9
9.0
9.0
6.3
3.8
0.0
0 Å
13 Å
Sequence

Full Protein Sequence

>P04062|GBA1_HUMAN|L444P mutant (precursor 536 AA)

MEFSSPSREECPKPLSRVSIMAGSLTGLLLLQAVSWASGARPCIPKSFGYSSVVCVCNATYCDSFDPPTFPALGTFSRYESTRSGRRMELSMGPIQANHTGTGLLLTLQPEQKFQKVKGFGGAMTDAAALNILALSPPAQNLLLKSYFSEEGIGYNIIRVPMASCDFSIRTYTYADTPDDFQLHNFSLPEEDTKLKIPLIHRALQLAQRPVSLLASPWTSPTWLKTNGAVNGKGSLKGQPGDIYHQTWARYFVKFLDAYAEHKLQFWAVTAENEPSAGLLSGYPFQCLGFTPEHQRDFIARDLGPTLANSTHHNVRLLMLDDQRLLLPHWAKVVLTDPEAAKYVHGIAVHWYLDFLAPAKATLGETHRLFPNTMLFASEACVGSKFWEQSVRLGSWDRGMQYSHSIITNLLYHVVGWTDWNLALNPEGGPNWVRNFVDSPIIVDITKDTFYKQPMFYHLGHFSKFIPEGSQRVGLVASQKNDPDAVALMHPDGSAVVVVLNRSSKDVPLTIKDPAVGFLETISPGYSIHTYLWRRQ
Pocket-lining residues: ARPCDSFRMMEL
Data Assets

Downloadable Files

E_ij Matrix (.npy)
data/results/GBA_L444P/E_ij_matrix_MT10_pocket1.npy
E_ij Matrix (.csv)
data/results/GBA_L444P/E_ij_matrix_MT10_pocket1.csv
Transient Conformation (.pdb)
data/results/GBA_L444P/conformations/mt_10.pdb
Pocket Summary (.json)
data/results/GBA_L444P/MT10_pocket1_summary.json
Stage 3 Candidates (.json)
data/results/GBA_L444P/stage3_chaperone_candidates.json
← Back to Database
REFOLD · S.Y.A.L.I.S Labs · Aaryan Senthilvanan