Abstract:
Fueled by advances in computing power, algorithm development, and AI, we are witnessing a transformation in how we understand cellular machines and discover new medicine. I will discuss three projects from my lab that harness this transformation to address fundamental challenges in understanding protein structure-function relationships, membrane-dependent pharmacology, and allowing proteomewide ligand discovery. Human Hv1 is a prototypical voltage- and pH-gated channel wrapped in mystery. I will showcase how we elucidate its activation mechanism using state-of-the-art all-atom continuous constant pH molecular dynamics (CpHMD) simulations and AlphaFold models. Second, I will present the first atomic simulations of membrane permeation processes for realistic ionizable drug molecules (opioids) using the weighted-ensemble CpHMD method. Together with cell-level experiments, the data suggest membrane permeation as a major driver for the extreme in vivo potency of fentanyl. Finally, I will discuss the first multimodal AI Protein Profiling (AiPP) platform that leverages chemical proteomic data and protein language models for proteomewide ligand design. AiPP enabled the first atlas of reversible and cysteine-directed covalent ligand binding sites in the human proteome.
Biography:
Jana Shen was born in Shanghai, China. She earned Diplom Chemie from Bergische Universität Wuppertal in Germany before pursuing graduate study in quantum chemistry, obtaining a PhD from University of Minnesota. Her postdoctoral work at the Scripps Research Institute was focused on the development of MD algorithms. Jana is a developer of the widely used CHARMM and AMBER MD packages. Her lab's developments of the CpHMD methods have enabled a wide range of applications that have deepened the mechanistic understanding of proton-coupled processes of proteins and materials. Jana served as the American Chemical Society (ACS) COMP division chair in 2022 and became an ACS Fellow in 2025. Dr. Shen currently serves as North America Editor-in-Chief of Journal of Computational Chemistry.
Seminar Series by the NYU-ECNU Center for Computational Chemistry at NYU Shanghai
This event is open to the NYU Shanghai, NYU, ECNU community and the computational chemistry community.