To enhance the development of Shenzhen Bay Laboratory (SZBL)’s research teams, support innovative researches and encourage interdisciplinary cooperation, the SZBL launched Shenzhen Bay Scholars Programme in 2021. The Shenzhen Bay Scholars Programme comprises three categories: “Shenzhen Bay Distinguished Scholar”, “Shenzhen Bay Scholar”, and “Shenzhen Bay Fellow”, in which, the “Shenzhen Bay Fellow” is designed to cultivate and support a group of young scholars with strong academic background, exceptional innovative ability and significant growth potential, promoting the SZBL’s talent pipeline across various institutes/centers academic echelons and research teams, and encouraging bold and original scientific research and exploration.
"The persistence of quantum effects within cells seems absurd and counter-intuitive. However, if they do exist—as substantial evidence indicates in certain phenomena—then life must be operating in a uniquely special way."
—"Life on the Edge: The Coming of Age of Quantum Biology"
In 2008, Yangyi Lu, a freshman in Peking University's chemistry program, found himself fascinated by some intriguing issues he discovered in the library—why does quantum tunneling occur during biocatalysis? How can excitons in photosynthesis move like waves, sensing all paths to the reaction center and selecting the most efficient one? Besides molecules and atoms at the material level, what other hidden forces are at play in biological systems? Thus began his quest to unravel the deepest mysteries of nature.
"The fact that complex phenomena in chemistry and biology can be simulated using a few mathematical formulas and equations has always amazed me. This sense of wonder has continually driven me forward," said Lu. During his freshman and sophomore years, he intentionally took numerous courses in mathematics and physics. "I have always enjoyed reading alone, particularly captivated by the strange phenomena depicted in quantum science. When I encountered quantum chemistry in college, I was instantly hooked." With the rapid advancement of computational technologies in recent decades, many traditional fields have begun to explore new research models that integrate experimental and computational simulations. In his junior year, Lu joined the theoretical and computational chemistry lab at Tsinghua University, where he started his research training. Unlike traditional research methods that focus on experiments, theoretical and computational chemistry relies heavily on computer simulations using highly accurate quantum chemical methods. This multidisciplinary field blends knowledge from mathematics, physics, chemistry, and computer science. After two years of lab work, Lu's future research direction became clear, and the interdisciplinary scientific background he established during his undergraduate years solidified his future research. After graduation, he joined Professor Dongping Zhong's lab at Ohio State University for his doctoral program and research.
Professor Dongping Zhong's lab is renowned for its comprehensive analysis of molecular mechanisms of DNA repair by a photoenzyme called photolyase. Lu began his studies on quantum effects in the biological functions of proteins, including photolyase. At the microscopic molecular level, many protein functions involve electron/proton transfer reactions, which exhibit significant quantum effects due to the small masses of these particles. Some key biochemical reactions would not occur without these quantum effects. The lab's specialized techniques enabled the observation of these quantum effects in biological systems. By analyzing experimental data, Lu developed a theoretical model of quantum reaction dynamics for protein functions, adding a crucial piece to the understanding of molecular reactions in biology.
However, biological systems are exceedingly complex, comprising not only macromolecules like proteins and DNA but also other molecules like water and ions. Simulating quantum effects in biochemical reactions requires highly accurate quantum chemical methods. The QM/MM (Quantum Mechanics/Molecular Mechanics) method successfully integrates high-precision quantum chemistry with efficient molecular dynamics simulations to model complex biochemical processes. This innovative approach won the Nobel Prize in Chemistry in 2013. However, most QM/MM methods assume a single electronic ground state. Many biological systems, such as DNA repair, photosynthesis, and respiration, often involve multiple electronic states. Quantum chemical methods for simulating multiple electronic-state systems require extremely high computational demand, and there are many theoretical difficulties in combining this kind of methods with molecular dynamics methods. There are only a few research groups in the world that can compute and simulate these complex systems.
In 2021, Yangyi Lu was invited to join the Institute of Systems and Physical Biology of Shenzhen Bay Laboratory (SZBL) to develop quantum chemical simulation methods. "This year, we have made significant progress and established a rigorous theoretical framework called Multi-State Density Functional Theory (MSDFT), capable of simulating multiple electronic excited states simultaneously," Lu explained. This method overcomes the limitations of Kohn-Sham Density Functional Theory, which can only simulate the ground state. Additionally, while time-dependent density functional methods calculate single excitation energies, MSDFT provides a universal approach for simulation of arbitrary electronic excited states. Meanwhile, several SZBL research groups have integrated Information Technology (IT) and Biotechnology (BT) to develop a comprehensive computational software platform, called Qbics, which now includes MSDFT and molecular dynamics simulation modules.
Concerning his research aims, Lu said, "In the short term, we aim to work with Dr. Jun Zhang, the lead developer of Qbics, to merge MSDFT with molecular dynamics simulations to study complex chemical and biological systems. In the long-term, we aspire to establish an efficient research team, collaborating with experimental groups to tackle major scientific challenges and achieve practical applications. By uncovering the microscopic reaction mechanisms of enzyme functions, we can inspire drug research labs to find suitable targets for diseases and design effective drug molecules. For instance, studies of DNA repair aids in skin cancer treatment research, and investigating photoreceptor proteins connects closely with the field of opto-genetics."
Lu believes that the SZBL, with its dynamic environment and an average employee age of 31, is an exciting and rapidly growing research institution. For early-career scholars like himself, SZBL offers ample startup funding, freedom, and strong support. "The SZBL has its own supercomputer cluster, which is a rare asset. We have the resources to test methods and simultaneously perform quantum simulations of chemical reactions and biological macromolecules without worrying about computational limitations. Conducting scientific exploration in such environment, I am feeling very happy." Lu remarked.
Biography
Yangyi Lu earned his B.Sc. degree from Peking University in 2012 and Ph.D. degree in Physical Chemistry from Ohio State University in 2018. From 2018 to 2021, he conducted postdoctoral research at Ohio State University and collaborated with the Center of Ultrafast Science and Technology at Shanghai Jiao Tong University on photo-biological research. In the fall of 2021, he joined the Institute of Systems and Physical Biology at the SZBL and was awarded the "Shenzhen Bay Fellowship” in 2022. His research focuses on theoretical and computational chemistry, with interests in quantum biology, electronic structure methods, and quantum molecular reaction dynamics. He has published over ten papers as the first or corresponding author in journals such as Nat. Commun., J. Phys. Chem. Lett., and J. Chem. Theory Comput.
