Publications

2019

Zapp C, Obarska-Kosinska A, Rennekamp B, Mercadante D, Barayeu U, Dick TP, Denysenkov V, Prisner T, Bennati M, Daday C, Kappl R, Gräter F (2019). Mechanoradicals in tensed tendon collagen as a new source of oxidative stress. Accepted on Nature Communications.
Bauer MS, Baumann F, Daday C, Redondo P, Durner E, Jobst MA, Milles LF, Mercadante D, Pippig DA, Gaub HE, Gräter F, Lietha D (2019). Structural and mechanistic insights into mechanoactivation of focal adhesion kinase. Proceedings of the National Academy of Science 116(14): 6766-6774.

2018

Zosel F, Mercadante D, Nettels D, Schuler B. (2018). A Proline Switch Explains Kinetic Heterogeneity in a Coupled Folding and Binding Reaction. Nature Communications 9(1):332.
Irani AH, Mercadante D, Williams MAK. (2018). On the Electrophoretic Mobility of Partially Charged Oligosaccharides as a Function of Charge Patterning and Degree of Polymerization. Electrophoresis 39(12), 1497-1503.
Tan PS^#, Aramburu IV^#, Mercadante D^#, Tiagi S, Chowdhury A, Spitz D, Shammas SL, Gräter F, Lemke EA. (2018). Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors. Cell Reports, 22(13), 3660-3671.
Mercadante D, Gräter F, Daday C. (2018). Conan: A Tool to Decode Dynamical Information from Molecular Interaction Maps. Biophysical Journal.114(6), 1267-1273.

2017

Sénéchal F, Habrylo O, Hocq L, Domon JM, Marcelo P, Lefebvre V, Pelloux J*, Mercadante D*. (2017). Journal of Biological Chemistry. 292(52), 21538-21547.
Mercadante D*, Wagner JA, Aramburu IV, Lemke EA, 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.
Fuertes G, Banterle N, Ruff KM, Chowdhury A, Mercadante D, Koehler C, Kachala M, Girona GE, Milles S, Mishra A, Onck PR, Gräter F, Esteban-Martín S, Pappu RV, Svergun DI, Lemke EA. (2017). Decoupling of size and shape fluctuations in heteropolymeric sequences reconciles discrepancies in SAXS vs. FRET measurements. Proceedings of the National Academy of Sciences 114(31), E6342-6351.

2016

Irani AH, Owen JL, Mercadante D, Williams MAK. (2016). Molecular dynamics illuminate the role of counterion condensation in polyelectrolyte transport. (2017). Biophysical Journal 110(3), 592a.
Dugard CK, Mertz, RA, Rayon C, Mercadante D, Hart C, Benatti MR, Olek AT, San Miguel PJ, Cooper BR, Wolf-Dieter R, McCann MC, Carpita NC. (2016). The cell wall arabinose-deficient Arabidopsis thaliana mutant murus5 encodes defective allele of reversibly glycosylated polypeptide2. Plant Physiology 171(3), 1905-1920.
Tursch A, Mercadante D, Tennigkeit J, Gräter F, Özbek S. (2016). Minicollagen cysteine-rich domains encode distinct modes of polymerization to form stable nematocyst capsules. Scientific Reports 6; 25709.
Kent L, Loo TS, Melton LD, Mercadante D, Williams MAK, Jameson GB. (2016). Structure and properties of non-processive, salt-requiring, acidophilic pectin methylesterases from Aspergillus niger provide insights into the key determinants of processivity control. Journal of Biological Chemistry 291(3), 1289-1306.
Milles S^#, Mercadante D^#, Valle Aramburu I^#, Ringkjøbing Jensen M, Banterle N, Koehler C, Clarke J, Shammas S, Blackledge M, Gräter F, Lemke E.A. (2016). Plasticity of an ultrafast interaction between nucleoporins and nuclear transport receptors. Cell 163(3), 734-744.

2015

Beckmann A, Xiao S. Müller JP, Mercadante D, Nüchter T, Kröger N, Langhojer F, Petrich W, Holstein T, Benoit M, Gräter F, Özbek S. (2015) A fast recoiling silk-like elastomer facilitates nanoseconds nematocyst discharge. BMC Biology 13, 3.
Wagner J, Mercadante D, Nikič I, Lemke EA, Gräter F. (2015). Principles of bio-orthogonality in strain promoted click reactions. Chemistry: A European Journal 21(35), 12431-12435.
Mercadante D*, Milles S, Fuertes G, Svergun D, Lemke EA, Gräter F. (2015). Kirkwood-Buff rescues the over-collapse of a disordered protein in canonical protein force fields. Journal of Physical Chemistry B 119(25), 7975-7984.

2014

Mercadante D, Melton LD, Jameson GB, Williams MAK. (2014) Processive pectin methylesterase: the role of electrostatic potential, breathing motions and bond cleavage in the rectification of Brownian motions. PLoS One 9(2), e87581.

2013

Cover Page Biophysical Journal 2013

Mercadante D*, Melton LD, Jameson GB, Williams MAK, 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.

2012

Cover Page Biophysical Journal 2012

Mercadante D, Melton LD, Loo T, Norris GE, Williams MAK, Dobson RCJ, Jameson GB. (2012). Bovine β-lactoglobulin is dimeric under imitative physiological conditions: dissociation equilibrium and rate constants over the pH range 2.5 to 7.5. Biophysical Journal 103(2), 303-313.

^#Equally shared first authorship. *Corresponding authorship**.

Featured Research

We are interested in a broad set of questions that target the understanding and the design of molecular systems. Our approaches are based on the use of the so-called computational microscope. ### As a microscope is powered by light and a lens, our microscope is fuelled by the laws of physics, the potential energy functions and parameters that make up force fields. Thanks to this we can investigate how the dynamics of molecules is linked to their function at a high level of resolution.

Study of Intrinsic disorder in the context of genetic transcription

Intrinsically disordered proteins (IDPs) do not naturally fold into 3D structures but they are key in a myriad of cellular processes. Disordered proteins perform ensemble-mediated rather than structure-mediated functions and their lack of structure gives them unconventional properties, like the ability to function at the centre of signalling hubs binding a moltitude of molecular partners (molecular promiscuity). They are centerpieces of genetic transcription and we study how disorder enables the formation of complexes that ultimately regualate gene-reading. To do so, we use a combination of computational approaches, encompassing molecular modelling and molecular dynamics simulations, heavily interfacing our results with single-moleucule experiments, which we outsource from collaborations.
How do post-translational modifications regulate protein affinity?

One of the main strategies to regulate proteins activitiy is to modify them after they have been expressed in cells. Since they occur after protein expression, these modification as called post-translational. Post-translational modifications (PTMs) consist in the addition/removal of chemical groups to/from amino acid sidechains in key positions along the protein sequence. Knowing how the occurrence of post-translational modification impacts the function of proteins is key to understand how dynamics regulates function. In the long term, this understanding might reveal opportunities to desire protein-like polymers with highly tunable properties for a set of applications.
Protein design to co-evolutionary approaches

Protein structure and dynamics has been shaped by evolution and the fitness of protein sequences is optimised by the set of functions a protein must fulfil and within the micro-environment it operates. Recently, models that can predict the fitness of a protein sequence have become more and more efficient. Such predictions are often coupled to the analysis of protein homologous sequences and can be used to even generate sequences with a higher fitness. Those sequences are candidates for applications outside cells, like industrial applications where their usage needs to be coupled to higher temperatures or pressure. With our research, we will exactly this need: aiming to discover protein sequences with a higher fitness through co-evolutionary based design.
Study of molecular motors "without fuel".

Molecular motors are able to convert chemical energy into mechanical energy or vice-versa. Other molecular motors are powered by an ion gradient, such as the rotary motor that synthesises ATP. Still other motors are powered by the free energy released when a nucleotide triphosphate is hydrolysed. The more processive a motor is the more unidirectional is the motion gleaned from the chemical free-energy released. In these motors, the free energy released constitutes a Brownian ratchet, preventing the reverse process. Remarkably, a class of enzymes called pectin methylesterase (PME) is involved in the processing of polysaccharide chains in plants, behaving as molecular motors that do not use high-energy exogenous co-substrates for their action, but carry the free energy for the Brownian ratchet endogenously. Understanding how PMEs achieve this, will lay the basis for the design of PME isoforms with enhanced or reduced processivity. Ultimately enhancing industrial processes and targeting events with serious economic downturns, such as plant parasitism and crop infection, in which PMEs play a big role.
What defines pH-dependent specificity for substrates in proteins?

The sequence-to-structure relationship in proteins define their ability to work in a specific microenvironment. A particular class of enzymes that modifies carbohydrates into the plant cell wall is particularly redundant in plant genomes. Plants express a large number of different isoforms for the same protein, which by a series of sequence variations can act specifically at different pH values. We investigate the molecular determinants of this specificity by relating molecular dynamics, position and protonation of protonatable residues.

Our Team

"We are always looking for motivated students and postdocs to join the lab! If you are interested, please send an email to Davide directly and enquire about potential opportunities!"

Davide Mercadante

Group Leader

Contact Davide by e-mail

Education and training:
BSc/MSc: Naples, Italy., PhD: Auckland, Postdocs: Heidelberg, Zurich

Hometown:
Naples, Italy.

Favourite (and only!) football team:
SSC Napoli

Favourite food:
Pasta and Pizza..what else?

Raina Chand

PhD candidate

Contact Raina by e-mail

Education and training:
BSc Hons: The University of Auckland.

Hometown:
Suva, Fiji.

Favourite activity outside the lab:
Watching reality tv (especially kuwtk and rhobh)

Favourite food:
Anything Japanese

Lynne Sun

Hons Student

Contact Lynne by e-mail

Education and training:
BSc: The University of Auckland.

Hometown:
Shanghai, China.

Favourite activity outside the lab:
Hanging out with friends and family

Favourite food:
Nachos and Sushi

Vanessa Ung

Hons Student

Contact Vanessa by e-mail

Education and training:
BSc: The University of Auckland.

Hometown:
Auckland, New Zealand.

Favourite musical:
Hamilton

Favourite activity outside the lab:
Hiking/Swimming on a sunny day or a good book on a rainy day

Jordan McIvor

PhD Student

Contact Jordan by e-mail

Education and training:
BSc Hons: The University of Canterbury.

Hometown:
Christchurch, New Zealand.

Favourite activity when not simulating:
Running and Skiing!

Favourite food:
Coffee and Chocolate

Veronika Laskova

PhD Student

Contact Veronika by e-mail

Education and training:
BSc/MSc: Masaryk University (Brno, Czech republic)

Hometown:
Ivaň, Czech republic

Favourite activity when not simulating:
Tramping, mountaineering (newbie), skiing and snowboarding!

Favourite food:
Steak, wine and coffee!

Junqi Bai

MSc Student

Contact Junqi by e-mail

Education and training:
BSc: Shanghai Institute of Technology (Shanghai, China)

Hometown:
Hohot, Inner Mongolia, China

Favourite activity when not simulating:
Listening to (pop!) music

Favourite food:
Hotpot!

News

JULY 2020

We are very happy to announce that Veronika Laskova is a new PhD student in the lab! She comes all the way from the Czech Republic but has fallen in love with NZ and decided to stay for longer! She will study some interesting molecular motors belonging to the 'carbohydrate world'..Welcome to the group Veronika!

JUNE 2020

Exciting news for the group, Jordan McIvor previously a student at the University of Canterbury joins us a PhD student. She will study, using a combination of computational methods, the effects of post-translational modifications on the dynamics and function of chromatin-binding proteins. Welcome Jordan! We all hope you'll enjoy the much warmer Auckland weather!

After few weeks of isolation and caution, moving across few emergency levels NZ has been declared Covid19-free and we are "back in business"! Looking forward to the start of few more projects in the upcoming weeks!

APRIL 2020

We have all moved into our "bubbles" to stop the spread of Covid-19 in New Zealand. However, we are all working remotely to cope as best as we can with the current situation still having fun with Science!

MARCH 2020

Vanessa Ung joins the lab! She will complete her Hons investigating the behavior of some intrinsically disordered proteins in very peculiar microenvironments!! Welcome Vanessa!

Welcome to Lynne Sun, which joins the lab for her Hons! Lynne will design and test the stability of new sequences 'evolved' from natural proteins via co-evolutionary approaches. Welcome to the lab!

Welcome to the Mercadante Group Page

We study molecular dynamics and link it to molecular function

Our group

reconstructs dynamics of molecules by using a diverse set of computational strategies and ultimately comparing our findings with the ones coming from experiments in a highly multidisciplinary environment. Our microscope is the computer, which allow us to obtain a lot of information at once.

By simulating the dynamics of a molecule, we can:

Molecualr simulations greatly increase the resolution range of experiments, help formulating new hypothesis by predicting molecular behaviour and have a crucial role for formulating new strategies to tackle scientific problems.