Pranam Chatterjee (University of Pennsylvania): “Discrete Generative Models for Programmable Molecule Design”

Abstract:

The Chatterjee Lab at the University of Pennsylvania develops discrete generative models that design functional biologics directly from sequence. Our work spans a new class of algorithms that unify discrete diffusion, flow matching, and Schrödinger bridge formulations for controllable, multi-objective molecular generation. Beginning with masked discrete diffusion frameworks such as PepTune, SOAPIA, NOSIE, Metalorian, and MemDLM, we demonstrated that discrete denoising processes can generate peptides, nanobodies, and membrane proteins with experimentally validated functionality. We then extended this paradigm through flow-based optimization, where models like Gumbel-Softmax Flow, MOG-DFM, and AReUReDi perform Pareto-efficient multi-objective design of therapeutic molecules across competing biochemical properties such as binding, solubility, and stability. Finally, our recent Schrödinger-bridge frameworks (BranchSBM, EntangledSBM, and ScooBDoob) formulate molecular and cellular dynamics as optimal transport between distributions, enabling the simulation, control, and design of protein folding and cell-state transitions. Together, these advances establish a unified sequence-based foundation for programmable biologic design, linking diffusion, flow, and bridge theories to the creation of next-generation therapeutic peptides and proteins.

Biography:

Pranam Chatterjee is an Assistant Professor of Bioengineering and Computer and Information Science and the Africk-Lesley Distinguished Scholar of Innovation at the University of Pennsylvania. His Programmable Biology Group develops new discrete generative models for the de novo design of peptide and protein biologics, spanning from algorithmic theory to pre-clinical validation in vitro and in vivo. The lab specifically develops therapeutic interventions for rare neurodegenerative diseases, pediatric sarcomas, viral infections, infertility, and substance use disorders. Having received his SB, SM, and PhD from MIT, Professor Chatterjee has received the NIH’s MIRA Award, Hartwell Individual Biomedical Research Award, and multiple NIH and foundation grants for his work. He has also co-founded Gameto, Inc., UbiquiTx, Inc., and AtomBioworks, Inc., which translates his research into fertility-related solutions, cancer therapeutics, and RNA medicines, respectively.

Zoom: https://upenn.zoom.us/j/95189835192, Passcode: 797599