Past Research Projects

FRET methodology

Förster resonance energy transfer has been widely used to measure the proximity of molecules, structural changes within macromolecules, as a signal of biochemical events or as a sensor of local conditions. We used this method to gain quantitative structural information and also developed ways to make the measurement of FRET efficiencies more precise. Interpreting FRET methods can also be complicated due to the presence of multiple fluorophores with unknown orientations. We created a framework to aid this interpretation with numerical analysis and molecular simulation.

Collaborators: Niko Hildebrandt, University of Rouen ; Kasia Walczewska-Szewc, Nicolaus Copernicus University

Key publications:
C Chen, B Corry, L Huang, N Hildebrandt. FRET-modulated multi-hybrid nanoparticles for brightness-equalized single-wavelength barcoding. J Am Chem Soc 141: 11123-11141, 2019. Online manuscript
A flexible approach to the calculation of resonance energy transfer efficiency between multiple donors and acceptors in complex geometries. Biophys. J. 89:3822-3836, 2005. pdf
Determination of the orientational distribution and orientation factor for transfer between membrane bound fluorophores using a confocal microscope. Biophys. J. 91:1032-1045, 2006. pdf
Quantitative FRET efficiency measurements using simultaneous spectral unmixing of excitation and emission spectra. J. Biomed. Optics., 8: 026024, 2013. Online manuscript

Mechanisms of ion selectivity

Many biological molecules, including channels, transporters, enzymes, macrocycles and DNA selectively bind or transport ions. Although ion selectivity is critical to the function of most molecules, the physical mechanisms by which it arises are not well understood. While we are particularly interested in understanding the origins of ion selectivity in biological channels, many of the principles involved in these proteins apply in other cases as well. By comparing the results of detailed simulations on a range of systems and developing model systems in which different mechanisms can be teased out we are not only explaining selectivity in each particular case, but also slowly gaining an appreciation of the many ways selective binding can arise and the conditions in which each is important. Although fundamental in nature, this research helps to explain the functioning of a number of critical molecules in human biology and lays the foundation for future innovation in biomedical research.

Collaborators: Dylan Jayatilaka, UWA ; Juanjo Nogueira, Autonomous University of Madrid

Key publications:
J J Nogueira, B Corry. Ion channel permeation and selectivity. In Oxford handbook of neuronal ion channels A Bhattacharjee (ed) Oxford Uni Press 2019. Online manuscript
Mechanism of ion permeation and selectivity in a voltage gated sodium channel. J Am Chem Soc, 134: 1840-1846, 2012. Online manuscript
Mapping the Importance of Four Factors in Creating Monovalent Ion Selectivity in Biological Molecules. Biophys. J. 100: 60-69, 2011. pdf , supp info
The predominant role of coordination number in potassium channel selectivity. Biophys. J. 93:2635-2643, 2007. pdf
Mechanisms of valence selectivity in biological ion channels. Cellular and Molecular Life Sciences. 63: 301-315, 2006. pdf
B Corry, TW Allen, S Kuyucak, SH Chung. Mechanisms of Permeation and Selectivity in Calcium Channels. Biophys. J. 80, 195-214, 2001. pdf

Nanotube membranes for desalination and filtration

Desalination of sea water via reverse osmosis is an attractive means of obtaining potable water, but one of its main drawbacks is the energy and cost required to force the water through semi-permeable membranes that block the passage of the salt. The energy costs could be reduced, however, there is possibility for new membranes to be developed with continuous pores that offer less resistance to water. Many narrow biological pores do just this: a pore of a given radius surrounded by non-polar atoms can allow for water to pass, but impede the passage of ions. Our research has shown that membranes formed from synthetic pores that mimic these biological channels, such as carbon nanotubes, can be used in desalination. Not only has this work shown that such membranes could significantly reduce the energy cost of reverse osmosis, it has determined the exact dimensions of the pores that are required and the effect of chemical functionalisation.

Collaborators: Mainak Majumder, Monash; Andrea Schäfer, Edinburgh

Key publications:
A Computational Assessment of the Permeability and Salt Rejection of Carbon Nanotube Membranes and their Application to Water Desalination. Phil. Trans., 374: 20150020, 2016. Online manuscript
Water and ion transport through functionalised carbon nanotubes: implications for desalination technology. Energy Env Sci, 4: 751-759, 2011. pdf
Designing carbon nanotube membranes for efficient water desalination. J. Phys. Chem. B. 112:1427-1434. 2008. pdf Cover picture
An intrinsic ion selectivity of narrow hydrophobic pores. J. Phys. Chem. B. 113: 7642-7649, 2009. pdf

Monitoring ion channel gating

Conformation changes are critical to the function of many proteins yet are difficult characterise at an atomic level. To better understand these structural alterations we combined experimental methods with simulation in order to characterise protein states that are hard to study by other methods. We are also using modern free energy simulation methods to map out the structural changes of a range of channel forming proteins. We are particularly intersted in the family of bacterial mechanosensitive channels that form safety valves that protect cells from hypo-osmotic shock, opening a wide pore under membrane tension to relieve excessive turgor pressure within the cell. By combining fluorescence measurements with molecular dynamics and coarse grained simualtions we were able to propose a structure of the open state of the protein and to examine the functions of various protein domains.

Collaborators: Boris Martinac, VCCRI

Key publications:
An improved open channel structure of MscL determined from FRET confocal microscopy and simulation. J Gen Physiol. 136: 483-494, 2010. pdf
Ion conduction in ligand gated ion channels: Brownian dynamics studies of four recent crystal structures. Biophys. J. 98: 404-411, 2010. pdf
An energy efficient gating mechanism in the acetylcholine receptor channel suggested by molecular and Brownian dynamics. Biophys. J. 90: 799-810, 2006. pdf

Dynamics in organic crystals

Molecular dynamics simulations provide a way to investigate the motions of atoms in crystals via the calculation of each individual atoms trajectory. We are interested in studying the atomic vibrations and reorientations of part or all of a molecule that affect bulk properties of the material, and understanding disorder that affects structure refinement. We are particularly interested in porous crystalline structures, examining the behaviour of guest molecules within porous hosts using simulation strategies with the long term aim of finding materials that can selectively transport guests for application in gas separation and storage.

Collaborators: Mark Spackman, UWA; Birger Dittrich Göttingen

Key publications:
Molecular dynamics simulations of structure and dynamics of organic molecular crystals. Phys Chem Chem Phys, 45: 14916-14929, 2010. pdf
Temperature dependence of rotational disorder in a non-standard amino acid from X-ray crystallography and molecular dynamics simulation, Phys. Chem. Chem. Phys., 11: 2601-209, 2009. pdf
Simulations of guest transport in clathrates of Dianin's compound and hydroquinone. Chem Eur J, 19: 2676–2684, 2013. Online manuscript