Understand molecular function and how interactions between molecules function. Predict molecular properties in different micro-environmental conditions. Design strong binders for known macromolecules. Design new molecules with enhanced function.
Tian P, Lemaire A, Sénéchal F, Habrylo O, Antonietti V, Sonnet P, Lefebvre V, Marin FI, Best RB, Pelloux J, Mercadante D*. Design of a Protein with Improved Thermal Stability by an Evolution-Based Generative Model. Angewandte Chemie International Edition.
McIvor JAP, Larsen DS, Mercadante D*. (2022) Simulating Polyproline II-Helix-Rich Peptides with the Latest Kirkwood–Buff Force Field: A Direct Comparison with AMBER and CHARMM. The Journal of Physical Chemistry B 126(40): 7833-7846.
Daday C, de Buhr S, Mercadante D, Gräter F. (2022) Mechanical force can enhance c-Src kinase activity by impairing autoinhibition. Biophysical Journal 121(5): 684-691.
Safran J#, Ung V#, Bouckaert J, Habrylo O, Molinie R, Fontaine JX, Lemaire A, Voxeur A, Pilard S, Pau-Roblot C, Mercadante D, Pelloux J, Senechal F. The structural, dynamical and biochemical characterizations of Verticillium dahliae pectate lyase, VdPelB, highlight its specificities. bioRxiv 2022
Safran J#, Tabi W#, Ung V#, Lemaire A, Habrylo O, Bouckaert J, Rouffle M, Voxeur A, Pongrac P, Bassard S, Molinie R, Fontaine JX, Pilard S, Pau-Roblot C, Bonnin E, Larsen DS, Morel-Rouhier M, Girardet JM, Lefebvre V, Senechal F, Mercadante D, Pelloux J (2022) Differences in the structure of plant polygalacturonases specify enzymes dynamics and processivities to fine-tune pectins and root development. bioRxiv 2022
Hocq L, Habrylo O, Voxeur A, Pau-Roblot C, Safran J, Sénéchal F, Fournet F, Bassard S, Battu V, Demailly H, Tovar JC, Pilard S, Marcelo P, Savary BJ, Mercadante D, Njo MF, Beeckman T, Boudaoud A, Pelloux J, Lefebvre V. (2021). The pH-dependent processivity of Arabidopsis AtPME2 can control cell wall mechanical properties biorXiv
Sullivan MP, Cziferszky M, Tolbatov I, Truong D, Mercadante D, Re N, Gust R, Goldstone DC, Hartinger CG. Probing the Paradigm of Promiscuity for N‐Heterocyclic Carbene Complexes and their Protein Adduct Formation. Angewandte Chemie International Edition. 60(36): 19928-19932.
Safran J, Habrylo O, Cherkaoui M, Lecomte S, Voxeur A, Pilard S, Bassard S, Pau-Roblot C, Mercadante D, Pelloux J, Sénéchal F. New insights into the specificity and processivity of two novel pectinases from Verticillium dahliae. International Journal of Biological Macromolecules 176: 165-176.
Bjarnason S, Ruidiaz SF, McIvor J, Mercadante D, Heidarsson PO. (2021). Protein intrinsic disorder on a dynamic nucleosomal landscape Progress in molecular biology and translational science. 183: 295-394.
Heidarsson PO, Mercadante D, Sottini A, Nettels D, Borgia MB, Borgia A, Kilic S, Fierz B, Best RB, Schuler B. Disordered proteins enable histone chaperoning on the nucleosome. biorXiv
Mercadante D. (2019). Getting structures into gear: a computational microscope to discover, understand and design molecular function. The International Symposium on Macrocyclic and Supramolecular Chemistry.
Mercadante D. (2019). Advancements in the Understanding of Pectin Methylesterase Enzymes and Their Inhibitors for Use in Food Science Applications. Encyclopedia of Food Chemistry, Volume 3, 202-208. Published by Elsevier 2019.
Mercadante D. (2019). Intrinsically Disordered Proteins: Polymers Without Structure but With Great Potential for Applications in Food Science. Encyclopedia of Food Chemistry, Volume 3, 134-140. Published by Elsevier 2019.
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.
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.
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.
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.
#Equally shared first authorship. *Corresponding authorship.
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.
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 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.
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.
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.
Education and training:
BSc/MSc: Naples, Italy., PhD: Auckland, Postdocs: Heidelberg, Zurich
Favourite (and only!) football team:
Pasta and Pizza..what else?
Education and training:
BSc Hons: The University of Auckland.
Auckland, New Zealand.
Favourite activity outside the lab:
Hiking/Swimming on a sunny day or a good book on a rainy day
Education and training:
BSc Hons: The University of Canterbury.
Christchurch, New Zealand.
Favourite activity when not simulating:
Running and Skiing!
Coffee and Chocolate
Education and training:
BSc: The University of Auckland.
Tauranga, New Zealand.
Favourite activity when not simulating:
Going sailing and making sourdough!
- Our latest work on how nucleosomes can be remodelled thanks to competitive substitution of intrinsically disodered chaperones has finally been published in Nature Chemistry! The article has been overall well-received in the community and beyond! It hopes to provide insights how, thanks to disordered proteins, tight molecular interactions can be regulated within timescales acceptable for life..happy reading! The article can be accessed here
- Davide has become the director of the Scholars Programmes at The University of Auckland. He's looking forward to bring his contribution to the growth and constant improvements of these flagship programmes of the university.
- Congratulations to Davide for being awarded a Riddet Institute PhD Scholarship! The project will oversee the computational design of new proteins with appeal for the Food industry. The PhD position will be advertised soon!
- Congratulations to Junqi Bai for completing her MSc in Chemistry in our group! Junqi looked at the conformational ensembles of peptides obtained from milk proteins upon tripsin digests! We wish Junqi all the best for her upcoming PhD!
- We are delighted to announce that Summer Wong has joined the group for her Hons projects! Summer, in collaboration with the Selenko group at the Weizmann Institute of Science will study the behaviour of αSynuclein: a protein involved in the onset of Parkinson's disease. Welcome Summer!
- Because of her excellent performance in her Hons degree and project, Vanessa Ung has been awarded a MSc scholarship from the University of Auckland! Vanessa is now a MSc student in the Mercadante group! Congratulation Vanessa, well-deserved!
- Congratulations to Lynne Sun and Vanessa Ung for succesfully completing their Hons degrees! We are now looking forward to your graduation day during the southern emisphere winter! It will be a sunny day no matter if it rains! Congrats!
- Congratulations to Davide for being appointed review editor of Structural Biology, within the specialty section of Frontiers in Molecular Bioscience, Cell and Developmental Biology. Davide is looking forward to contribute to the publication of excellent work contributing to our understanding of molecular behaviour...
- 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!
- 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!
- 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!
- 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!