JAMUN: Transferable Molecular Conformational Ensemble Generation with Walk-Jump Sampling

They are not well characterized as single structures as has traditionally been the case, but rather as ensembles of structures with an ergodic probability distribution(Henzler-Wildman & Kern, 2007). Protein motion is required for myglobin to bind oxygen and move it around the body (Miller & Phillips, 2021). Drug discovery on protein kinases depends on characterizing kinase conforma-tional ensembles (Gough & Kalodimos, 2024). The search for druggable'cryptic pockets' requires understanding protein dynamics, and antibody design is deeply affected by conformational ensembles (Colombo, 2023). However, while machine learning (ML) methods for molecular structure prediction have experienced enormous success recently, ML methods for dynamics have yet to have similar impact. ML models for generating molecular ensembles are widely considered the'next frontier' (Bowman, 2024; Miller & Phillips, 2021; Zheng et al., 2023).