We hypothesized the binder will have better success rate when designed to bind the position where natural binder has contact to, and with a more hydrophobic residue. This method performs de novo binder generation using a four-stage AlphaFold-guided design pipeline procided in Bindcraft. It begins by hallucinating a binder sequence against a chosen target interface using AFDesign, optimizing sequence and structure simultaneously to satisfy hotspot contacts, foldability, and geometric constraints. The top trajectory structures are then evaluated with full AlphaFold-Multimer predictions to obtain reliable confidence and interface metrics. High-quality trajectories are passed to ProteinMPNN for sequence redesign and stabilization, followed by a second AlphaFold-Multimer validation of the redesigned binders. Final designs are scored using structural, energy, and interface metrics (including pLDDT, iPTM, iPAE, dG/dSASA, shape complementarity, packing, and clash checks) to select binders with stable folds and well-defined interfaces.
id: wild-gecko-vine

Nipah Virus Glycoprotein G
0.79
80.46
--
9.6 kDa
76
id: golden-bee-opal

Nipah Virus Glycoprotein G
0.79
83.00
--
16.5 kDa
138
id: mellow-bee-lotus

Nipah Virus Glycoprotein G
0.78
60.56
--
9.7 kDa
78
id: solid-orca-pearl

Nipah Virus Glycoprotein G
0.76
87.88
--
19.1 kDa
158
id: radiant-mole-wave

Nipah Virus Glycoprotein G
0.72
79.50
--
16.5 kDa
138
id: rough-bear-granite

Nipah Virus Glycoprotein G
0.71
86.05
--
19.2 kDa
158
id: quiet-moth-clay

Nipah Virus Glycoprotein G
0.70
59.74
--
16.3 kDa
135
id: deep-toad-ash

Nipah Virus Glycoprotein G
0.70
83.02
--
19.3 kDa
157
id: golden-dove-fern

Nipah Virus Glycoprotein G
0.51
85.29
--
15.5 kDa
125
id: bright-tiger-crystal

Nipah Virus Glycoprotein G
0.36
76.19
--
9.4 kDa
76