Theoretical Biophysics Group, Dept. of Physics, UIUC

To Students Contemplating Research in Theoretical Biophysics

ATP Synthase, the Ultimate Molecular Motor

Every day, an active graduate student synthesizes her/his body weight equivalent of the molecule ATP from a molecule ADP. The energy content in ATP is used by the body to drive numerous biochemical syntheses as well as mechanical processes like muscle action and brain processes. ATP synthase contains two coupled molecular motors: one (F0) which converts an electrical membrane potential into a torque, the other (F1) which converts a torque into chemical synthesis. Both motors are studied in the Theoretical Biophysics Group through several approaches, quantum electronics of ATP synthesis, simulation of protein dynamics, and stochastic modeling of long-time protein processes. The ATP synthase research team of the Theoretical Biophysics Group seeks another graduate student to join this work.

Interactive Molecular Dynamics

The increase of computer power through parallel computing combined with the strength of our group in molecular dynamics and graphics programming has brought about a new approach to the study of the molecular machines in living cells, interactive molecular dynamics. This methodology permits researchers to visually connect to an ongoing simulation of a biomolecular machine and manipulate it in real user time in order to test hypotheses of its function. First research projects are being accomplished now, one on studying the transport of sugars through membrane channels, another to investigate the docking of cytochrome c2 to the photosynthetic reaction center to donate an electron. A new application will study the transport of chloride through a membrane ion channel. The project provides a superb opportunity in advancing computing technology, but also basic physics: the manipulation generates irreversible work (IW) that needs to be discounted to reveal the thermodynamic potential (TP) underlying the process being studied. The possibility for the computation of TP from IW has only recently been proven in an elegant theory on non-equilibrium statistical mechanics that we will exploit.

Quantum Biology of Vision and Entangled State Problem

Since Newton, vision has attracted physicists seeking to explain how light is sensed by organisms. Recently, the structure of a visual receptor protein has been solved crystallographically (Science 289:739-745, 2000) and physicists are again called upon to explain the fundamentals of vision, how quantum mechanics serves living systems to see the world. The Theoretical Biophysics Group has studied over the last twenty years a bacterial analogue of visual receptors, bacteriorhodopsin, that actually uses light absorption to electrically charge cell membranes. A new thesis project is based on a very recent methodological breakthrough in our group: we are now capable to calculate quantum-chemically the forces the visual chromophore retinal experiences in the excited state reached after light absorption. This can be done while the molecular dynamics simulation describes the motion of the chromophore-protein system. We need to address now the dynamics of jumps between excited and ground states at moments when the two states approach each other energetically. Surface hopping poses a fundamental problem in quantum mechanics closely related to the core problem in quantum computing: the retinal at the moment of hopping is in an entangled state (linear combination of ground and excited state) that relaxes quickly to a non-entangled state. This relaxation process, due to electron-phonon coupling needs to be properly described in the framework of our new generation of photodynamics simulations.

Development of a Protein Scaffold System for Lipid Nanodisks

This is a close collaboration with the group of Steve Sligar, UIUC Biochemistry. Based on previous work in the Theoretical Biophysics Group and recent advances in the Sligar group in designing a scaffold protein (SP) from the Apo A1 motifs we will structurally model scaffold proteins produced genetically in the Sligar group and possibly redesign them. We will also investigate the immersion of membrane proteins in the lipid-SP disks to guide and help analyze experiments. Lastly, we will attempt to design lipid-SP systems that crystallize. This project offers an opportunity for purely theoretical work, but also the fascinating opportunity to combine experimental and theoretical work.

Single Molecule Electrical Recording

This project is a close collaboration between two experimental groups, the Soft Condensed Matter group of Alexey Bezryadin (UIUC Physics) and the nanodevice group of Greg Timp (UIUC Electrical and Computer Engineering), and two theoretical groups, the nanodevice group of Jean-Pierre Leburton (Computational Electronics Group at Beckman Institute), and the Theoretical Biophysics Group. The project will manufacture a 20 Angstrom pore in silicon that is lined with two nanodevices for measurement of AC current and AC fields along the pore with submicrosecond time constants. Proteins and DNA will be pulled through the pore and electrical properties recorded. The device will be simulated and an analysis of the relationship between recorded data and molecular properties developed. This project provides opportunities for both purely theoretical and purely experimental works, as well as combined experimental and theoretical studies.