Alan Mark

Biography

After my PhD I held postdoctoral positions at the RSC (ANU) (1987-1988) and at the University of Groningen (1989-1990). In 1990 I moved with W.F. van Gunsteren to ETH Zurich becoming Oberassistant in 1996. In 1998 I was appointed Professor of Biophysical Chemistry, University of Groningen. In 1998 I was awarded the Swiss Ruzicka Prize for research in Chemistry. In 2004 I was awarded an Australian Research Council (ARC) Federation Fellowship and joined The University of Queensland in 2005. In 2011 I was awarded a University of Queensland Vice Chancellor's Senior Research Fellow. I am also an affiliate of the Institute of Molecular Biosciences at UQ and the Australian Infectious Diseases Research Centre.

Research Interest

Physical and Computational Chemistry - Simulation of biomolecular systems The group focuses on understanding and predicting the macroscopic (experimentally observable) properties of biomolecular systems such as proteins, nucleic acids and lipid aggregates, in terms of the interactions between atoms. In particular our work concentrates on the development of tools (i.e. simulation software, atomic force fields, theoretical models and experimental techniques) that can be used to understand and predict the physico-chemical basis of interactions and dynamic processes within biomolecular systems. Specific areas of interest include structure prediction, protein and peptide folding, the self-assembly of protein/lipid complexes and the calculation of thermodynamic properties such as ligand binding affinities. Protein Folding Understanding how proteins fold is one of the grand challenges of modern biology. The failure of proteins to fold correctly is also linked to a range of debilitative diseases including Alzheimer’s disease, BSE and some forms of Type II diabetes where misfolded proteins form destructive aggregates called amyloid fibrils. Research on folding is conducted at multiple levels. Small model systems such as antimicrobial peptides are used to refine force fields and simulation techniques. On a larger scale we are simulating how multiple copies of certain peptides aggregate in order to understand how amyloid fibrils form. Cell Surface Receptors How the binding of a molecule to an extracellular receptor transfers a signal across the cell membrane or how changes in the environment can activate certain cell surface receptors are both critical question in cell biology. To address such issues we are investigating the mechanism by which low pH triggers the activation of the Dengue E protein, which plays a critical role in the entry of the virus into cells. We are also investigating the structural changes associated with the binding of human growth hormone to the growth hormone receptor. Membrane Protein Assembly Cell membranes are the archetypal self-organised supramolecular structure. Membrane protein complexes also represent a new frontier in structural biology. Using simulations, we are able to directly investigate how bilayers and vesicles form. We are also investigating the assembly of functional structures such as the assembly of anti-microbial peptides into transmembrane pores. This in turn is being used to understand the mechanism by which larger complexes form in heterogeneous environments. Computational Drug Design Work in computational drug design is focused in two areas. The development of an automated topology build to provide atomic descriptions of drug like molecules, the development of novel methods for estimating the free energy of binding and for the refinement of non-standard ligand molecules in X-ray crystal complexes. Research Projects Simulating peptide folding and assembly Pore-forming peptides as models for protein assembly The nucleation and growth of amyloid fibrils Mechanism of activation of the human growth hormone receptor New methods in drug design Secondary Research Areas: Medicinal Chemistry Nanotechnology and Materials Chemistry