Imagine assembling a few thousand marbles into a machine capable of transforming the energy of an electric field into mechanical torque at nearly 100% efficiency and lasting ten million cycles. Although marbles are not atoms, Nature has done exactly that, assembling carbon, oxygen, nitrogen, and hydrogen atoms into remarkable nanomachines. And while Nature took billions of years to transform primordial dirt into the molecular motors that power living cells, the atoms comprising present-day “biomachines” are no different from those found in common inorganic compounds, and they obey the same laws of physics that enable the machines’ amazing properties. Understanding how the remarkable functionality of biological nanomachines comes about from the spatial arrangement of their atoms and using this knowledge to design synthetic systems that exceed in the performance of their biological counterparts is the focus of this group's research program.
DNA systems and genome replication. DNA is, arguably, the most celebrated molecule of life. Yet, its physical properties are poorly understood, and their role in processes of biological significance is unclear. This thrust of our research program uses computer modeling techniques to characterize physical properties of DNA and elucidate molecular processes that govern DNA replication and repair in bacteria and genome packaging and ejection in viruses.
Nanopores for single molecule detection and manipulation. Within just a decade from pioneering work demonstrating the utility of nanopores for molecular sensing, the field exploded with proposals for using nanopores as sensors, reactors, actuators, transducers, transporters, and other nanodevices Within the last five years, our work in this area has focused on developing a method for sequencing DNA, using solid-state nanopores for single-molecule force spectroscopy, and developing general methods for molecular simulations of such systems.
Micromechanics of cellular machinery. My long-term goal in this area is to elucidate the general physical mechanisms that biomolecular machines use to transform a sequence of chemical reactions into a unidirectional mechanical motion. A prototypical molecular motor is a calcium pump (SERCA) of sarcoplasmic reticulum that transports calcium ions against a concentration gradient by utilizing energy created by ATP hydrolysis. The conformations of this exemplary molecular motor are known at several states of the calcium pumping cycle. Connecting the structural states through a causal pathway that leads from ATP hydrolysis to transport of calcium is one of the greatest challenges in computational molecular biology, which we plan to tackle through a combination of new computational approaches to the problem.
Biomimetic systems. Our interests in this research field lie in the design and proof-of-principle demonstration of synthetic systems that have biological functionality.
