Research Interests

We study and develop chemical reactions of biomolecules based on physical principles.

(1) Charges and dipoles within biomolecular structures can generate strong local electric fields, accelerating chemical reactions by several orders of magnitude. By combining spectroscopic measurements with computational simulations, we elucidate local electric fields in the microenvironments of living systems and uncover how electrostatic environments regulate and govern biological catalysis, covalent modification, and covalent inhibition.

(2) Confining or recruiting reactive groups into spatial proximity can markedly enhance reaction rates. Leveraging proximity effects, we develop efficient and selective chemical reactions and biomolecular labeling strategies, and design new covalent warheads and covalent drugs.

(3) Mechanical forces can input energy into chemical reactions. We engineer protein-based molecular machines and develop mechanosensitive molecular modules to enable mechanical manipulation of biomolecules and to create mechanically gated chemical reactions.

Centered on electrostatic environments, proximity effects, and mechanical forces, we aim to uncover the physical foundations of life’s chemical processes and ultimately advance life science research and improve human health.

我们基于物理原理研究并开发生物分子的化学反应。

(1)  生物分子结构中的电荷和偶极可产生强局部电场，将化学反应加速多个数量级。我们结合光谱测量和计算模拟，解析活体体系微环境中的局部电场，揭示静电环境在生物催化、共价修饰与共价抑制中的关键作用和调控规律。

(2)  将反应基团限制或募集至空间邻近区域，可显著提升反应速率。我们利用邻近效应开发高效、特异的化学反应与生物分子标记方法，设计新型共价弹头和共价药物。

(3)  机械力能够为化学反应输入能量。我们利用工程化的蛋白质机器，并开发响应机械力的分子模块，实现对生物分子的力学操控，开发力学门控的化学反应。

围绕静电环境、邻近效应、机械力，我们致力于揭示生命反应的物理基础，推动生命科学研究并服务人类健康。