A significant amount of protein function requires binding small molecules,
including enzymatic catalysis. As such, designing binding pockets for small
molecules has several impactful applications ranging from drug synthesis to
energy storage. Towards this goal, we first develop HarmonicFlow, an improved
generative process over 3D protein-ligand binding structures based on our
self-conditioned flow matching objective. FlowSite extends this flow model to
jointly generate a protein pocket's discrete residue types and the molecule's
binding 3D structure. We show that HarmonicFlow improves upon the
state-of-the-art generative processes for docking in simplicity, generality,
and performance. Enabled by this structure modeling, FlowSite designs binding
sites substantially better than baseline approaches and provides the first
general solution for binding site design.

该论文介绍了利用 HarmonicFlow 和 FlowSite 两种改进的生成过程，通过结构建模和流匹配目标来提高蛋白质结合小分子的生成过程，并展示了其在蛋白质结合位点设计中的应用优势。