Dr Davide Mercadante

Doctor of Philosophy

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Senior Lecturer


  • 2019-Present Senior Lecturer, School of Chemical Sciences, The University of Auckland, Auckland, New Zealand.
  • 2017-2019 Postdoctoral Fellow, The University of Zurich, Zurich, Switzerland. 
  • 2013-2017 Postdoctoral Fellow, Heidelberg Institute of Theoretical Studies and Heidelberg University, Heidelberg, Germany. 
  • 2008-2012 PhD in Chemistry, The University of Auckland, Auckland, New Zealand.
    • 2009-2010 EMBO short-term fellow, Cambridge University, Cambridge, United Kingdom. 
  • 2006-2008 MSc in Pharmaceutical Biotechnology, University Federico II, Naples, Italy. 
  • 2001-2005 BSc in Medical Biotechnology, University Federico II, Naples Italy. 

I obtained my BSc and MSc degrees in biotechnology, from the University Federico II in Naples, Italy. I then travelled to New Zealand, and graduated with a PhD in chemistryat the University of Auckland, where I performed research revolving around the integration of computational and experimental approaches.

After the PhD, I moved back to Europe for my post-doctoral experience, first in Germany and then in Switzerland. 

In Germany, I worked at the Heidelberg Institute for Theoretical studies, getting specialised in the study of the conformational dynamics of macromolecules using molecular simulations. 

In Switzerland I worked at The University of Zurich,  where I integrated my computational knowledge with single-molecule Förster Resonance Energy Transfer (smFRET) spectroscopy experiments performed in living cells. 

In 2019, I moved back to New Zealand at to the School of Chemical Sciences of The University of Auckland as Senior Lecturer, where I undertake research in computational biophysics of macromolecular systems, strictly integrating simulations and experiments. 

Research | Current

My group aims to understand how the dynamics of molecules, specifically macromolecules, regulate their function. The group employs several approaches to achieve this, adopting methodological frameworks of statistical mechanics such as molecular dynamics or Monte Carlo simulations. Our simulations are rigorously complemented with experiments to achieve a reliable understanding of the simulated ensembles and to exploit the power of simulations in predicting and designing molecular behaviour. 

The group investigates macromolecular dynamics and interactions at different levels of structural details: from all-atom to several degrees of coarse-graining. 

Often, we combine several simulation strategies to understand different facets of molecular behaviour. These simulation strategies encompass un-biased and biased molecular dynamics or re-weighting of the simulated ensemble, according to experimental findings; to ultimately reach the maximum agreement between experimental and computational investigations.

Overall, the activities of the group revolve around interconnecting themes, with a vision that can be summarized with the statement: “Understand to design, block or improve”.


Theme 1: Understanding the principles regulating dynamics-driven molecular interactions, function or dysfunction. 

Dynamical behaviour is a ubiquitous property of macromolecules and is intrinsically linked to function. Since molecules are tiny and work in thermal baths, structure and dynamics have therefore evolved together. 

The computational workflows we design and adopt, aim to simulate and analyse dynamical features of molecules to elucidate how the molecular function is mediated by the fluctuations within the molecules and how such a dynamical behaviour is linked to the ability of defining conformations and interactions with other molecules. We therefore study molecules in isolation and in complex with other molecular partners. 

In contrast to experiments, which mostly monitor a single or a small series of observables, simulating the dynamics of a molecule yields a particularly high-dimensional observable: which is defined by the positions, the velocities and the forces of each particle constituting a molecular system. The set of atomic positions overtime constitutes a molecular dynamics trajectory, from which other quantities linking to the function of the simulated molecule can be calculated. 


Theme 2: Modify and conquer. How chemical modifications of macromolecules can be used to regulate their physico-chemical properties?  

The chemistry behind the building units of Nature, which can be amino acids (for proteins), nucleotides (for nucleic acids) and other monomers (such as monosaccharides, lipids, etc.) is multifaceted. However, Nature additionally holds a large range of tricks to expand the functional repertoire of molecules even more: for example, nucleotides in nucleic acids can undergo a series of chemical modifications such as addition of methyl groups along the chain (methylation), or addition of multiple adenosine monophosphate units (polyadenylation). Amino acids in proteins undergo an even wider set of (post-translational) modifications, including methylation, phosphorylation, alkylation, glycosylation, etc.

But how do these modifications affect dynamics? And then function? Do they form or break additional interactions? And more relevantly, are there general rules that we can extract from the addition of small chemical groups to building blocks of life and use them to tune functional dynamics of polymers used for everyday applications? 

In other words, can we learn the working rules on which Nature operates and design from such first principles? 


Theme 3: Simulate and improve. Using molecular simulations to design active compounds

Macromolecule-ligand interactions are at the very core of life and pathologies, which are very often targeted by the design of small molecules that bind certain molecular targets and either block or re-activate them. 

On the other hand, by interacting with specific partners inside our organism, bioactive and nutraceutical compounds naturally improve cellular physiology, providing important health benefits, often working in the direction of preventing the occurrence of disease. 

Nevertheless, the development of new “binders”, for whatever purpose, is a long and obstacle-filled process. Within this process, simulations, which wholly take into account the dynamics of molecular targets, can be powerful predictors of targetable conformational states and initiators of new designs of existing drug molecules. We combine our understanding of molecular dynamics as outlined in Theme 1, with the work of teams of experimental scientists to design new compounds that aim to improve cellular physiology.

For more info please visit the group’s website: Mercadante group webpage.

Postgraduate supervision

I am actively looking for motivated people that bear research interests at the interface between experimental and computational work, in line with the research philosophy of the group. Students will acquire skills encompassing chemistry and chemical biology, scripting and programming and will become proficient in High-Performance Computing on nation-wide supercomputing facilities both in New Zealand and overseas. This will ensure that, while the members of team will become productive within the research themes of the group, they will acquire transferable skills that will boost their future employability. 


Major Grants: 

  • (November 2019) Marsden Fast Start Grant titled “Looking at the dark side of the proteome: how do post-translational modifications control highly disordered proteins for the regulation of genetic transcription?”. Role in the application: Principal investigator researcher. Awarded amount for three years research: NZD$ 300,000.
  • (November 2018) Full Marsden grant titled “Pectin methylesterase: tuning pectin function with complex variation upon a simple theme”. Role in the application: Affiliated investigator. Awarded amount to be split in 3 years: NZD$ 935,000.

Nominations and Awards

  • (2019) Awarded of a Fast-start Marsden Grant as Principal Investigator.
  • (2018) Awarded of a Full Marsden Grant as Associated Investigator.
  • (2017) Nominated for the IUPAP C6 2017 Awards in Biological Physics.
  • (2015) Awarded a prize for excellent research at the Heidelberg Institute for Theoretical Studies for the contribution to the understanding of intrinsically disordered protein behaviour.
  • (2015) Nominated for the Postdoctoral Award from the Biophysical Society, Intrinsically disordered Proteins subgroup.
  • (2014-2016) Awarded a 2-years BIOMS Post-doctoral fellowship from the Interdisciplinary Centre for Scientific Computing (IWR) of University of Heidelberg – Germany.
  • (2013-2014) Awarded a 1-year Post-doctoral research scholarship from the Heidelberg Institute of Theoretical Studies (HITS) – Germany.
  • (2010) Awarded a prize for outstanding research from the University of Auckland Department of Chemistry Research Showcase, New Zealand.
  • (2009) Awarded an EMBO short-term fellowship to study the binding of pectin methylesterase enzymes with differently methylated pectin polymers at the University of Cambridge, UK. Valued at ~€ 8000.
  • (2009) Awarded a 3-year PhD international scholarship at The University of Auckland, Auckland, New Zealand.
  • (2008) Awarded a 3-year PhD research fellowship from the Riddet Institute, Centre of Research Excellence, Palmerston North, New Zealand. 

Areas of expertise

  • Biological Chemsitry
  • Food Science
  • Computational Biophysics
  • Molecular dynamics and Monte Carlo simulation methods

Committees/Professional groups/Services

  • Auckland Branch Editor of the New Zealand Institute of Chemistry (NZIC) Journal. 
  • Member of the Biophysical Society

Selected publications and creative works (Research Outputs)

  • Tan, P. S., Aramburu, I. V., Mercadante, D., Tyagi, S., Chowdhury, A., Spitz, D., ... Lemke, E. A. (2018). Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors. Cell reports, 22 (13), 3660-3671. 10.1016/j.celrep.2018.03.022
  • Mercadante, D., Wagner, J. A., Aramburu, I. V., Lemke, E. A., & Gräter F (2017). Sampling Long- versus Short-Range Interactions Defines the Ability of Force Fields To Reproduce the Dynamics of Intrinsically Disordered Proteins. Journal of chemical theory and computation, 13 (9), 3964-3974. 10.1021/acs.jctc.7b00143
  • Milles, S., Mercadante, D., Aramburu, I. V., Jensen, M. R., Banterle, N., Koehler, C., ... Blackledge, M. (2015). Plasticity of an ultrafast interaction between nucleoporins and nuclear transport receptors. Cell, 163 (3), 734-745. 10.1016/j.cell.2015.09.047
  • Mercadante, D., Milles, S., Fuertes, G., Svergun, D. I., Lemke, E. A., & Gräter F (2015). Kirkwood-Buff Approach Rescues Overcollapse of a Disordered Protein in Canonical Protein Force Fields. The journal of physical chemistry. B, 119 (25), 7975-7984. 10.1021/acs.jpcb.5b03440
  • Mercadante, D., Melton, L. D., Jameson, G. B., & Williams, M. A. K. (2014). Processive pectin methylesterases: the role of electrostatic potential, breathing motions and bond cleavage in the rectification of Brownian motions. PloS one, 9 (2)10.1371/journal.pone.0087581
  • Mercadante, D., Melton, L. D., Jameson, G. B., Williams, M. A. K., & De Simone, A. (2013). Substrate dynamics in enzyme action: rotations of monosaccharide subunits in the binding groove are essential for pectin methylesterase processivity. Biophysical journal, 104 (8), 1731-1739. 10.1016/j.bpj.2013.02.049
  • Mercadante, D., Melton, L. D., Norris, G. E., Loo, T. S., Williams, M. A. K., Dobson, R. C. J., & Jameson, G. B. (2012). Bovine β-lactoglobulin is dimeric under imitative physiological conditions: dissociation equilibrium and rate constants over the pH range of 2.5-7.5. Biophysical journal, 103 (2), 303-312. 10.1016/j.bpj.2012.05.041
  • Mercadante, D. (2012). Macromolecular interactions: pectin, pectin methylesterase and beta-lactoglobulin The University of Auckland. ResearchSpace@Auckland.
    URL: http://hdl.handle.net/2292/19607

Contact details

Primary office location

SCIENCE CENTRE 302 - Bldg 302
Level 8, Room 867
New Zealand