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

View all Publications

Supervision

View all Supervision

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.

View all Available Projects

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

  • Brooks, Andrew, Dai, W., O'Mara, M. L., Abankwa, D., Chhabra, Y., Pelekanos, R. A., Gardon, O., Tunny, K. A., Blucher, K. M., Morton, C. J., Parker, M. W., Sierecki, E., Gambin, Y., Gomez, G. A., Alexandrov, K., Wilson, I. A., Doxastakis, M., Mark, A. E. and Waters, M. J. (2016). Going downstream - how does GH binding activate JAK2. In: Annual Scientific Meeting of the Endocrine Society of Australia, Adelaide, Australia, (16-16). 23-26 August, 2015. doi:10.1111/cen.13010

  • Malde, Alpeshkumar K. and Mark, Alan E. (2015). 179 Validation of ligands in X-ray crystal structures. In: Book of Abstracts. Albany 2015: The 19th Conversation. The 19th Conversation, Albany/State University of New York, (117-117). 9-13 June 2015. doi:10.1080/07391102.2015.1032816

  • Koziara, Katarzyna B., Stroet, Martin, Malde, Alpeshkumar K. and Mark, Alan E. (2015). Validation and development of the force field parameters for drug and drug-like molecules. In: Biophysical Society 59th Annual Meeting, Baltimore, United States, (158A-158A). February 7-11, 2015. doi:10.1016/j.bpj.2014.11.869

  • Brooks, Andrew J, Chhabra, Yash, Abankwa, Daniel, O’Mara, Megan, Dai, Wei, Gardon, Olivier, Tunny, Kathryn A., Blucher, Kristopher M., Morton, Craig J., Parker, Michael W., Sierecki, Emma, Gambin, Yann, Guillermo A. Gomez, Alexandrov, Kirill Kirill, Doxastakis, Manolis, Mark, Alan E. and Waters, Michael J. (2014). A new cytokine receptor activation paradigm: Activation of JAK2 by the growth hormone receptor. In: SI: 2014 ICIS Abstract Issue, ICIS Conference. 2nd Annual Meeting of the International Cytokine and Interferon Society (ICIS), Melbourne, VIC Australia, (22-22). 26 - 29 October 2014. doi:10.1016/j.cyto.2014.07.227

  • Mark, Alan E. (2013). Understanding the Induction and Stabilization of Transmembrane Pores by Peptides. In: Abstracts of the 57th Annual Meeting of the Biophysical Society. 57th Annual Meeting of the Biophysical Society, Philadelphia Pa, (601A-601A). 02-06 February 2013. doi:10.1016/j.bpj.2012.11.3335

  • Canzar, Stefan, El-Kebir, Mohammed, Pool, Rene, Elbassioni, Khaled, Malde, Alpesh K., Mark, Alan E., Geerke, Daan P., Stougie, Leen and Klau, Gunnar W. (2012). Charge group partitioning in biomolecular simulation. In: Benny Chor, Proceedings: 16th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2012. 16th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2012, Barcelona, Spain, (29-43). 21 - 24 April 2012. doi:10.1007/978-3-642-29627-7_3

  • Yennamalli, RM, Kobe, B, Mark, AE, Young, PR and Subbarao, N (2009). Dengue viral envelope protein and histidine protonation. In: Indian Journal of Virology. XVIII National Conference of Indian Virological Society, Post Graduate Institute of Medical Education and Research, Chandigarh, India., (29-29). 11–13 December 2008.

  • Sengupta, D., Leontiadou, H., Mark, A. E. and Marrink, S. J. (2007). Molecular dynamics simulations of toroidal pores formed by antimicrobial peptides. In: Biophysical Journal: Annual Meeting Abstracts Issues. Biophysical Society 51st Annual Meeting, Bethesda, MA, (545A-545A). 3-7 March 2007.

  • Kampmann, T., Muller,, Robinson, J., Mark, A, Young, P R and Kobe, B (2006). The mechanism of vira membrane fusion and identification of novel antiviral lead compounds. In: 31st Lorne Conference on Protein Structure & Function. 31st Lorne Conference on Protein Structure & Function, Lorne, Victoria, Australia, (Abstract). 5-9 Feb, 2006.

  • de Vries, AH, Knecht, V, Yefimov, S, Mark, AE and Marrink, SI (2005). Simulations of phase transformations of lipid-water mixtures by molecular dynamics. In: Abstracts of Papers of the American Chemical Society. 230th National Meeting of the American-Chemical-Society, Washington Dc, (U1241-U1241). Aug 28-Sep 01, 2005.

  • Kovalskyy, DB, Dubina, VM, Mark, AE and Kornelyuk, AI (2005). Effect of distal mutations on the molecular dynamics of the HIV-1 protease. In: Febs Journal. IUBMB 50th Anniversary Symposium, Budapest Hungary, (143-143). Jul 02-07, 2005.

  • Kampmann, T., Muller, D. A., Robinson, J., Mark, A., Young, P. R. and Kobe, B. (2005). A structural model for low pH mediated viral fusion: The role of histidine protonation. In: 3rd Australian Virology Group Meeting. 3rd Australian Virology Group Meeting, Phillip Island, (Abstract). 9-12 Dec, 2005.

  • Marrink, SJ and Mark, AE (2005). Coarse grained simulation of phase transitions of lipid membranes. In: Biophysical Journal. 49th Annual Meeting of the Biopysical-Society, Long Beach Ca, (384A-384A). Feb 12-16, 2005.

  • Knecht, V, Marrink, SJ and Mark, AE (2005). Simulation studies of self-organization in lipid systems. In: Biophysical Journal. 49th Annual Meeting of the Biopysical-Society, Long Beach Ca, (384A-384A). Feb 12-16, 2005.

  • Mark, AE and Vangunsteren, WF (1995). Free energy calculations in drug design: A practical guide. In: New Perspectives in Drug Design. 9th International Round Table of the Rhone-Poulenc-Rorer-Foundation on New Perspectives in Drug Design, Turnberry Scotland, (185-200). Apr, 1994.

  • Vangunsteren, WF, Brunne, RM, Mark, AE and Vanhelden, SP (1992). Computer-Simulation of Biomolecules - Comparison with Experimental-Data. In: Molecular Aspects of Biotechnology : Computational Models and Theories. Nato Advanced Research Workshop On the Role of Computational Models and Theories in Biotechnology, Sant Feliu Guixols Spain, (105-122). Jun 13-19, 1991.

  • Vanhelden, SP, Vaneijck, BP, Mark, AE, Vangunsteren, WF and Janssen, Lhm (1992). Molecular-Dynamics and Free-Energy Perturbation Calculations On Complexes of Alpha-Cyclodextrins with P-Substituted Phenols, a Comparison Between Experiment and Simulation. In: Minutes of the Sixth International Symposium On Cyclodextrins. 6Th International Symp On Cyclodextrins, Chicago Il, (170-175). Apr 21-24, 1992.

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

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.