Professor Alan Mark

UQ Fellow

School of Chemistry and Molecular Biosciences
Faculty of Science

Affil Professorial Research Fellow

Institute for Molecular Bioscience
a.e.mark@uq.edu.au
+61 7 336 54180

Overview

We use computer based modelling techniques to understand and predict the the structural and dynamic properties of (bio)molecules including proteins and lipid aggregates.

Born in 1961, I obtained a BSc (Hon 1) at the University of Sydney in 1982. I obtained my PhD in 1986 from the John Curtin School of Medical Research, Australian National University (ANU), on the "Binding Responses Associated with Self-Interacting Ligands: Studies on the Self-Association and Receptor binding of Insulin”. After holding postdoctoral positions at the ANU, University of Groningen, The Netherlands and the Federal Institute of Technology (ETH), Zurich, Switzerland I was appointed Professor of Biophysical Chemistry (Molecular Simulation) University of Groningen, in 1998. In 1998 I also received the Swiss Ruzicka Prize for research in Chemistry for work on simulating peptide folding. In 2004 I was awarded an ARC Federation Fellowship and in February 2005 an honorary chair (Bijzonder Hoogleraar) at the University of Groningen, The Netherlands. I have given over 90 invited lectures at conferences and academic Institutions around the world as well as at a range of summer and winter schools on advanced simulation techniques.

In my research I have performed pioneering simulations of a variety of important biological phenomena, including some of the first atomic simulations of protein unfolding and the first simulations of reversible peptide folding in a realistic environment. In recent years my group performed some of the first atomic and near atomic simulations of the spontaneous aggregation of surfactant and lipid systems into micelles, bilayers and vesicles. These have enabled us, amongst other things, to elucidate the mechanism by which pores are induced within biological membranes in unprecedented detail. Over the last decade I have been intimately involved in the development of the GROMOS force field which is specifically tuned for protein and peptide folding simulations and as well as the development of models for a range of solvents including methanol and trifluoroethanol. I have also been responsible for the development of methodology for the calculations of the thermodynamic properties of biomolecular systems such as free energies of binding and hydration, as well as estimating entropic effects from simulations. Most recently, I have been responsible for the development of novel approaches to promote structure formation in protein folding simulations that can be used for the refinement of protein structures generated by ab initio or by homology methods. Finally, I am associated with two, internationally recognised, (bio)molecular simulation packages the GROningen Molecular Simulation library (GROMOS) and the GROningen Machine for Chemical Simulations (GROMACS).

Qualifications

  • Bachelor of Science (Honours), The University of Sydney
  • Doctor of Philosophy, Australian National University

Publications

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Supervision

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Available Projects

  • Cytolytic antimicrobial peptides form an integral part of the innate immune system of many vertebrates including man. These antimicrobial peptides act by binding to and disrupting bacterial cell membrane. They are highly specific and increasingly recognized as a potential source of novel antibiotic agents. A major limitation in the further development of AMPs in a therapeutic setting is that the mechanism by which these peptides discriminate between different classes of membranes is still poorly understood. The aim of this project is to use computer simulation techniques elucidate the mechanism of action of cytolytic peptides at an atomic level. Specifically to study their binding to the outer membrane of specific pathogenic bacteria and determine the key structural and physico-chemical properties that allows them to distinguish between the pathogenic intruder and host cells.

  • A critical consideration when modelling biomolecular systems is the description of the interactions. The aim of this project is to develop and validate an automated force field topology builder (ATB; http://compbio.biosci.uq.edu.au/atb/). The ATB provides force field descriptions for drug-like molecules for use in studying the ligand-macromolecule interactions with applications in drug design and X-ray refinement.

  • Lipid molecules are fundamental components of biological membranes. Not only do they play a role in the compartmentalization of cells and organelles but, also participate in fundamental processes such as cell division and intracellular trafficking. The aim of this project is to develop detailed models representing the membranes of specific cell types.

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Publications

Book Chapter

  • Poger, David and Mark, Alan E. (2013). Study of proteins and peptides at interfaces by molecular dynamics simulation techniques. In Juan M Ruso and Angel Pineiro (Ed.), Proteins in solution and at interfaces: methods and applications in biotechnology and materials science (pp. 291-313) Hoboken NJ, United States: John Wiley & Sons, Inc.. doi:10.1002/9781118523063.ch14

  • Chipot, C., Mark, A. E., Pande, V. S. and Simonson, T. (2007). Applications of Free Energy Calculations to Chemistry and Biology.. In Christophe Chipot and Andrew Pohorille (Ed.), Free Energy Calculations Theory and Applications in Chemistry and Biology (pp. 463-492) Berlin ; New York: Springer.

Journal Article

Conference Publication

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Cytolytic antimicrobial peptides form an integral part of the innate immune system of many vertebrates including man. These antimicrobial peptides act by binding to and disrupting bacterial cell membrane. They are highly specific and increasingly recognized as a potential source of novel antibiotic agents. A major limitation in the further development of AMPs in a therapeutic setting is that the mechanism by which these peptides discriminate between different classes of membranes is still poorly understood. The aim of this project is to use computer simulation techniques elucidate the mechanism of action of cytolytic peptides at an atomic level. Specifically to study their binding to the outer membrane of specific pathogenic bacteria and determine the key structural and physico-chemical properties that allows them to distinguish between the pathogenic intruder and host cells.

  • A critical consideration when modelling biomolecular systems is the description of the interactions. The aim of this project is to develop and validate an automated force field topology builder (ATB; http://compbio.biosci.uq.edu.au/atb/). The ATB provides force field descriptions for drug-like molecules for use in studying the ligand-macromolecule interactions with applications in drug design and X-ray refinement.

  • Lipid molecules are fundamental components of biological membranes. Not only do they play a role in the compartmentalization of cells and organelles but, also participate in fundamental processes such as cell division and intracellular trafficking. The aim of this project is to develop detailed models representing the membranes of specific cell types.

  • The activation of cell surface receptors such as the growth hormone receptor and the epidermal growth factor receptor is a critical step in cell regulation. Molecular dynamics simulation techniques will be used to characterize the conformational changes within the extracellular and transmembrane domains that accompany the binding of the cytokine (growth hormone1 or epidermal growth factor) to its receptor thereby shedding light on the mechanism of action of cytokine receptors in general.