(A) (D) Property Models &

Molecule Docking Program Pose Score Active Learning Optimization

Featurization

Inference
Generative Pose Score
Docking Program
ML “Surrogate” Model Model

Featurization

Inference
Compound ML “Surrogate” Model
Libraries

(B) (C)
Molecule Docking Program Pose Score Molecule Docking Program Pose

Filter Top N Molecules Experimental ML Rescoring Model

Data

ML “Surrogate” Model BFE prediction

(B)
Molecule Docking Program Pose Score

Collect Top N Molecules

ML “Surrogate” Model
 (A)

SMILES InChi Key

C1CN(CCC1N2C=NC3=CN=C4C(=C32)C=CN4)CC5=CC=CC=C5 WKWXJWGOAKGEEM-UHFFFAOYSA-N

(B)

A Scoring Functions
Chemguass4
GLIDE
AutoDockVina Position search
within binding pocket
Position search
within binding pocket
Position search
within binding pocket
Position search
within binding pocket

Retrieve best scoring Retrieve best scoring Retrieve best scoring Retrieve best scoring
(C) pose pose pose pose

Retrieve best n
(D) (E)
Retrieve best n Retrieve best
conformations conformation + pose,
along with its score

Protein- from the various

molecular
Return poses for
Virtual
Ligand bioinformatician conformations

Screening
Poses Rescore with final
scoring function

Return Score and

associate with
original ligand
 AmpC β-lactamases Surrogate Model RES

D
C