Design of AI-Enhanced Drug Lead Optimization Workflow for HPC and Cloud

Drug discovery is a costly process of searching for new candidate medications. Among its various stages, lead optimization easily consumes more than half of the pre-clinical budget. We propose an automated lead optimization workflow that uses data mining methods in components such as execution of molecular simulations, feature extraction, and clustering with convolutional variational autoencoder. The end-to-end execution produces protein-ligand binding affinity of atoms in the lead molecule which serves as metrics for identifying modifiable atoms. In contrast to known methods, our method provides new hints for drug modification hotspots which can be used to improve drug efficacy. Our workflow can potentially reduce the lead optimization turnaround time from months/years to several days compared with the conventional labor-intensive process and thus will become a valuable tool for medical researchers.