Understanding complex (bio)molecular systems using experiments alone is difficult. Computer simulations based on physical and chemical principles can complement experiments and provide novel mechanistic insights. We develop and apply state-of-the-art computational tools to explore the underlying mechanism of a broad range of complex systems. Enzymes and other biological macromolecules, along with bio-materials interfaces, are of primary interest.

  • Developing computational techniques and theoretical models for complex systems – A substantial amount of research activity in our group is geared toward developing novel theoretical and computational techniques to make the simulation of complex (bio)molecular systems possible. One major area involves improving the efficiency and accuracy of combined quantum mechanical and classical mechanical methods, such that bond-breaking and bond-formation (chemistry!) can be studied in detail for realistic chemical (e.g., at solid/liquid interface) and biological environments. Another area is related to the development of coarse-grained models for proteins and membranes, such that insights into the driving force of conformational transitions in proteins, protein/peptide assembly and membrane remodeling (e.g., membrane fusion/fission) can be obtained computationally. In these coarse-grained model developments, we explore both particle and continuum mechanics based models, and integration with both atomistic simulations and experimental observables such as thermodynamics data for complex solutions.
  • Simulation of complex molecular machines in bio-energy transduction – Biological systems involve many fascinating “molecular machines” that transform energy from one form to the other. Important examples are biomolecular motors and proton pumps, the former utilizes the proton motive force to synthesize ATP, while the latter employs the free energy of chemical reactions (e.g., oxygen reduction) to generate the proton motive force across the membrane. With recent developments in crystallography, cyro-EM and single molecule spectroscopy, the working mechanisms of these nano-machines are being discovered. To understand the energy transduction process at an atomic level, our group is developing and applying state-of-the-art computational techniques to analyze the detailed mechanisms of several large molecular complexes including: myosin, DNA repair enzymes and cytochrome c oxidase. Questions of major interest include: (i). What are the functionally relevant motions of these complexes? (ii). How are the chemical events (e.g., ATP binding and hydrolysis) coupled to the mechanical (e.g., conformational transition) process? (iii). How is the efficiency and vectorial nature of energy transduction regulated?
  • Interfacing biology and material science – The last decades have seen the thrilling developments in materials at the nanometer scale. Nano-materials with tailored electrical, optical or mechanical properties have been synthesized. An exciting direction that has been recently recognized is that biomolecules can be used to provide control in organizing technologically important (non-biological) objects into functional nano-materials. The interaction between biomolecules and inorganic materials is fundamental to these applications, and we are using computational techniques to investigate this aspect. These studies are expected to play a guiding role in the design of novel hybrid materials, new sensors for biological molecules, strategies for sustainable nano-technology, as well as in understanding the fascinating process of biomineralization.

Cui Group Website