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Marco De Vivo

Researcher TT (TT1)
Group Leader (PI)


+39 010 71781 577





2000 - Laurea (MSc) in Chemistry, Dept of Chemistry G. Ciamician, University of Bologna
2001 - 2004 - PhD in Pharmaceutical Chemistry - Dept of Pharmaceutical Chemistry, University of Bologna
2004-2007 - Postdoctoral Researcher for 3 years - Prof. M. L. Klein, at the University of Pennsylvania, Philadelphia, USA.


2015 - present Research Associate to the IAS-5 / INM-9 Computational Biomedicine Institute at the Forschungszentrum Jülich, Germany
2014 - present Group Leader (PI) of the Molecular Modeling and Drug Discovery Lab in IIT
2009 - 2013 Team Leader, Dept of Drug Discovery and Development, at the Italian Institute of Technology
2007 - 2009 Research Scientist for 27 months - Structure-based drug design group, Rib-X Pharmaceuticals (New Haven, CT-USA)
2004 - 2007 Postdoc for 3 years with Prof. M. L. Klein, at the University of Pennsylvania, Philadelphia, USA.
2003 Visiting Scientist for 5 months at the Swiss Federal Institute of Technology (ETH Zürich), Institute of Pharmaceutical Sciences
2001 - 2002 Visiting Scientist for 24 months at the International School for Advanced Studies (SISSA) in Trieste, Italy


More in detail:

I am Group Leader of the Molecular Modeling and Drug Discovery Lab in IIT
Since 2015, I am also affiliated as Research Associate to the IAS-5/INM-9 Computational Biomedicine Institute, Forschungszentrum Jülich, Germany.

In my research lines, I pursue my interest in enzymatic catalysis and drug discovery through the application of molecular modeling to study enzymes of pharmaceutical relevance. Toward this end, in our lab we integrate computational and medicinal chemistry to design, synthesize and test (in vitro) novel compounds. Results are fully integrated with structural, biochemical and pharmacological data to characterize function and inhibition of targeted enzymes, and perform structure-based drug discovery of new molecular entities potentially endowed with a desired pharmacological activity. 

I joined IIT from the structure-based drug design group of Rib-X Pharmaceuticals (New Haven, CT, USA) where I was involved in the design and development of next-generation antibiotics. This company was co-funded by Prof. W. Jorgensen of Yale University who is a leader in computational drug discovery. The opportunity to satisfy my interest in industrial drug discovery, together with the opportunity to work closely with Prof. Jorgensen’s group in a top level scientific environment, convinced me to join the structure-based drug design group at Rib-X. Under the direct supervision of Rib-X CSO Dr. Erin Duffy, I made key contributions to the discovery of novel compounds with antibacterial activity, coordinating the discovery effort and working in close collaboration with crystallographers, biochemists, medicinal chemists and pharmacologists.

I graduated in Chemistry in 2000 at the University of Bologna, in the group of Prof. A. Bottoni. 
In 2004 I obtained my Ph.D. in Pharmaceutical Sciences from the same institution, under the supervision of Prof. M. Recanatini. During my Ph.D., I spent 2 years at the International School for Advanced Studies in Trieste, in the group of Prof. P. Carloni, and few months at the ETH institute in Zurich in the group of Prof. L. Scapozza. My project was focused on the characterization of ligand binding and enzymatic catalysis of protein kinases by means of a variety of computational methods. Then, I was postdoctoral research associate at the Center for Molecular Modeling led by Prof. M. L. Klein, at the University of Pennsylvania (Philadelphia, USA), for 3 years. During my postdoctoral training, I investigated metalloenzymes of pharmaceutical interest, such as RNase H, with focus on their reactivity and ligand binding.




In our Lab, we focus on the study of catalysis and inhibition of pharmaceutically relevant enzymes. This is performed through the development and application of computational methods, which are integrated with experimental data. The atomic-level comprehension of enzymatic function is used to initiate drug discovery, where computational methods are combined with medicinal chemistry and molecular biology for the rational design and identification of promising compounds as potent enzyme inhibitors.

Enzymatic catalysis is studied by means of classical molecular dynamics simulations coupled with first-principles-based computational methods (e.g. QM/MM simulations) and enhanced sampling techniques for free energy estimation. This multiscale computational approach allows performing quantum enzymology and deciphering the key factors of catalytic reaction mechanisms. Then, this knowledge on the target of interest is used to perform docking, virtual screening, de novo small molecules computational design and in silico ADMET evaluation for structure-based drug design of potent enzyme inhibitors. Promising compounds are either purchased or synthesized in the Lab, and assayed to identify and optimize novel small molecules able to inhibit the enzymatic function of interest. The goal is to understand general principles that govern catalysis and use this information to design potent inhibitors as a promising starting point for drug discovery programs. 

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Marco De Vivo, PhD 


Laura Riccardi, PhD (junior postdoc in Computational Chemistry)

Jose Antonio Ortega Martínez, PhD (senior postdoc in Medicinal Chemistry)

Jose M. Arencibia, PhD  (senior postdoc - In Vitro/In Vivo Molecular Biology)

PhD Student

Vito Genna (Computational chemistry)

Giuseppina La Sala (Computational Chemistry)

Elirosa Minniti (Medicinal Chemistry)

Marco Borgogno (Medicinal Chemistry)



2010-2013 PhD student Giulia Palermo (went for a postdoc at EPFL - Group of Prof. U. Rothlisberger)

Oct 2012 - Dec 2013 Junior postdoc Marino Convertino (went for a postdoc at University of North Carolina at Chapel Hill with Prof. Dokholyan)


Former Visiting Student

Sebastián Franco Ulloa (Computational Chemistry), from the Universidad de los Andes - Bogotà, Colombia, group of Prof. Gian Pietro Miscione (Jan, 2016 -Aprl, 2016).


Selected Publications

* Indicates when MarcoDV is the only or joint corresponding author

36. G. La Sala, L. Riccardi, R. Gaspari, A. Cavalli, O. Hantschel, M. De Vivo*
"HRD motif as the central hub of the signaling network for activation loop autophosphorylation in Abl kinase"
J. Chem. Theory Comput., 2016 - Just Accepted (Link)

35. V. Genna, P. Vidossich, E. Ippolito, P. Carloni, M. De Vivo*
"A self-activated mechanism for nucleic acid polymerization catalyzed by DNA/RNA polymerases"
J. Am. Chem. Soc., 2016 - Just Accepted (Link)

34. M. Pavlin, G. Rossetti, M. De Vivo, P. Carloni
“Carnosine and Homocarnosine Degration Mechanisms by the Human Carnosinase Enzyme CN1: Insights from Multiscale Simulations”
Biochemistry, 2016 – 55 (19), pp 2772–2784 (Link)

33. V. Genna, R. Gaspari, M. Dal Peraro, M. De Vivo*
"Cooperative motion of a key positively charged residue and metal ions for DNA replication catalyzed by human DNA Polymerase-η"
Nucleic Acids Res., 2016, 44 (6): 2827-2836 (Link)
Cover Article for April 7 issue (Link)

32. M. De Vivo*, M. Masetti, G. Bottegoni, A. Cavalli
"Role of Molecular Dynamics and Related Methods in Drug Discovery"
 J. Med. Chem., 2016 - 59 (9), pp 4035–4061 (Link)
Perspective on the special issue "Computational Methods for Drug Discovery and Design"
F1000 Prime Recommended (two recommendations) (Link)

31. G. Palermo, A.D. Favia, M. Convertino, M. De Vivo*
"The Molecular Basis for Dual Fatty Acid Amide Hydrolase (FAAH)/Cyclooxygenase (COX) Inhibition"
ChemMedChem, 2016, Volume 11, Issue 12, Pages 1252–1258 (Link)

30. G. Palermo, E. Minniti, M. L. Greco, L. Riccardi, E. Simoni, M. Convertino, C. Marchetti, M. Rosini, C. Sissi, A. Minarini, M. De Vivo*
"An optimized polyamine moiety boosts potency of human type II topoisomerase poisons as quantified by comparative analysis centered on the clinical candidate F14512"
Chem. Comm., 2015, 51, 14310-14313 (Link)
Cover Article (Back cover, October 2015)

29.  G. Palermo, I. Bauer, P. Campomares, A. Cavalli, A. Armirotti, S. Girotto, U. Roethlisberger, M. De Vivo*
“Keys to lipid selection in FAAH catalysis: Structural flexibility, gating residues and multiple binding pockets”
PLoS Comput Biol, 2015, 11(6): e1004231 (Link)  
Cover Article for June 2015 (Link)

28.  G. Palermo, A. Cavalli, M.L. Klein, M. Alfonso-Prieto, M. Dal Peraro, M. De Vivo*
“Catalytic Metal Ions and Enzymatic Processing of DNA and RNA”
Accounts Chem. Res., 2015, Feb 17;48(2):220-8 (Link

27.  G. Palermo, P. Campomares, A. Cavalli, U. Roethlisberger, M. De Vivo*
“Anandamide hydrolysis in FAAH reveals a dual strategy for efficient enzyme-assisted amide bond cleavage via nitrogen inversion” 
J. Phys. Chem. B, 2015, Jan 22;119(3):789-801  (Link)
Special Issue: Prof. W.L. Jorgensen Festschrift

26.  D. Pizzirani, A. Bach, N. Realini, A. Armirotti, L. Mengatto, I. Bauer, S. Girotto, C. Pagliuca, M. De Vivo, M. Summa, A. Ribeiro, D. Piomelli
“Benzoxazolone-Carboxamides: Potent systemically active inhibitors of intracellular Acid Ceramidase”
Angew Chem Int Ed Engl. 2015, Jan 7;54(2):485-9 (Link)

25.  G. Palermo, U. Roethlisberger, A. Cavalli, M. De Vivo*
“Computational insights into function and inhibition of Fatty Acid Amide Hydrolase” 
Eur. J. Med. Chem., 2015, Feb 16;91:15-26 (Review) (Link)

24. G. Palermo, P. Campomares, M. Neri, D. Piomelli, A. Cavalli, U. Roethlisberger, M. De Vivo*
“Wagging the tail: essential role of substrate flexibility in FAAH catalysis”
J. Chem. Theory Comput., 2013, 9 (2), pp 1202–1213 (Link)

23. G. Palermo, M. Stenta, A. Cavalli, M. Dal Peraro, M. De Vivo*
“Molecular simulations highlight the role of metals in catalysis and inhibition of type II topoisomerase”
J. Chem. Theory Comput., 2013, 9 (2), pp 857–862 (Letter) (Link)
Cover Article - February 2013, Vol. 9 Number 2

22.  L. Bertolacci, E. Romeo, M. Veronesi, P. Magotti, C. Albani, M. Dionisi, C. Lambruschini, R. Scarpelli, A. Cavalli, M. De Vivo, D. Piomelli, G. Garau
“A binding site for non-steroidal anti-inflammatory drugs in Fatty Acid Amide Hydrolase"
J. Am. Chem. Soc., 2013, Jan 9;135(1):22-5 (Communication) (Link)

21. A.D. Favia, D. Habrant, R. Scarpelli, M. Migliore, C. Albani, S. M. Bertozzi, M. Dionisi, G. Tarozzo, D. Piomelli, A. Cavalli, M. De Vivo*
“Identification and characterization of carprofen as a multitarget Fatty Acid Amide Hydrolase/Cyclooxygenase inhibitor” 
J. Med. Chem., 2012, 55 (20), pp 8807–8826 (Link)

20. S. V. C. Vummaleti, D. Branduardi, M. Masetti, M. De Vivo, R. Motterlini, A. Cavalli
"Theoretical Insights into the Mechanism of Carbon Monoxide (CO) Release from CO-Releasing Molecules",
Chemistry - A European Journal, 2012, Vol. 18, Issue 30, 9267-9275 (Link)

19. A. Lodola, D. Branduardi, M. De Vivo, L. Capoferri, M. Mor, D. Piomelli, A. Cavalli
”A catalytic mechanism for cysteine N-terminal nucleophile hydrolases, as revealed by free energy simulations”,
Plos One, 2012, 7(2), e32397 (Link)

18. G. Palermo, D. Branduardi, M. Masetti, A. Lodola, M. Mor, D. Piomelli, A. Cavalli, M. De Vivo*
"Covalent inhibitors of fatty acid amide hydrolase: A rationale for the activity of piperidine and piperazine aryl ureas",
J. Med. Chem., 2011, 54 (19), pp 6612–6623 (Link)

17. M. De Vivo, G. Bottegoni, A. Berteotti, M. Recanatini,F.L. Gervasio, A. Cavalli
"Cyclin-dependent Kinases: Bridging their Structure and Function through Computations",
Future Medicinal Chemistry, 2011 Sep;3(12):1551-9 (Review) (Link)

16. D. Branduardi, M. De Vivo, N. Rega, V. Barone, A. Cavalli
"Methylphosphate dianion hydrolysis in solution characterized by path collective variables coupled with DFT-based enhanced sampling simulations", 
J. Chem. Theory Comput., 2011, 7, 539-543 (Letter) (Link)

15. M. De Vivo*
"Bridging Quantum Mechanics and Structure-Based Drug Design"
Front Biosci., 2011, Jan 1; 16: 1619-1633. (Review) (Link)

14. M. H. Ho, M. De Vivo, M. Dal Peraro, M. L. Klein
"Understanding the Effect of Magnesium Ion Concentration on the Catalytic Activity of Ribonuclease H through Computation: Does a Third Metal Binding Site Modulate Endonuclease Activity?"
J. Am. Chem. Soc., 2010, 132, 13702-13712. (Link)

13. M. H. Ho, M. De Vivo, M. Dal Peraro, M. L. Klein
"Unraveling the Catalytic Pathway of Metalloenzyme Farnesyltransferase through QM/MM Computation"
J. Chem. Theory Comput., 2009, 5, 1657-1666. (Link)

12. M. De Vivo*, M. Dal Peraro, M. L. Klein
"Phosphodiester Cleavage in Ribonuclease H occurs via an Associative Two-Metal-Aided Catalytic Mechanism"
J. Am. Chem. Soc., 2008 130(33),10955-62. (Link)
• Highlighted in JACS select 2008, 130 (50),16824–16827.

11. M. De Vivo, A. Cavalli, P. Carloni, M. Recanatini
"Computational Study of the Phosphoryl Transfer Catalyzed by a Cyclin-Dependent Kinase"
Chemistry - A European Journal, 2007 13(30), 8437-44. (Link)

1o. M. De Vivo*, B. Ensing, M. Dal Peraro, G. A. Gomez, D. W. Christianson, M. L. Klein
"Proton Shuttles and Phosphatase Activity in Soluble Epoxide Hydrolase"
J. Am. Chem. Soc., 2007, 129(2), 387-394. (Link)

9. M. Dal Peraro, K. Spiegel, G. Lamoureux, M. De Vivo, W. F. DeGrado, M. L. Klein
"Modeling the Charge Distribution at Metal Sites in Proteins for Molecular Dynamics Simulations"
J. Struct. Biol., 2007, 157(3), 444-453. (Link)

8. B. Ensing, M. De Vivo, Z. Liu, P. Moore, M. L. Klein
"Metadynamics as a Tool for Exploring Free Energy Landscape of Chemical Reactions"
Accounts Chem. Res., 2006, 39, 73. (Link)

7. M. De Vivo, A. Cavalli, G. Bottegoni, P. Carloni, M. Recanatini
"Role of Phosphorylated Thr160 for the Activation of the CDK2/Cyclin A Complex "
Proteins, 2006, 62, 89-98. (Link)

6. M. De Vivo*, B. Ensing, M. L. Klein
"Computational Study of Phosphatase Activity in Soluble Epoxyde Hydrolase: High Efficiency through a Water Bridge Mediated Proton Shuttle"
J. Am. Chem. Soc., 2005, 127(32), 11226-11227. (Communication) (Link)

5. A. Bottoni, G.P. Miscione, M. De Vivo
"A Theoretical DFT Investigation of the Lysozyme Mechanism. Computational Evidence for a Covalent Intermediate Pathway"
Proteins, 2005, 59, 118-130. (Link)
F1000 Prime Recommended (by Prof. A. Warshel) (Link)

4. A. Cavalli, G. Bottegoni, C. Raco, M. De Vivo, M. Recanatini
"A Computational Study of the Binding of Propidium to the Peripheral Anionic Site of Human Acetylcholinesterase"
J. Med. Chem., 2004, 47, 3991-3999. (Link)

3. E. G. Occhiato, A. Ferrali, G. Menchi, A. Guarna, G. Danza, A. Comerci, R. Mancina, M. Serio, G. Garotta, A. Cavalli, M. De Vivo, M. Recanatini
"Synthesis, Biological Activity, and Three-Dimensional Quantitative Structure-Activity Relationship Model for a Series of Benzo[c]quinolizin-3-ones, Nonsteroidal Inhibitors of Human Steroid 5alpha-Reductase 1"
J. Med. Chem., 2004, 47, 3546-3560. (Link)

2. A. Cavalli^, M. De Vivo^, M. Recanatini (^Co-first author)
"Density Functional Study of the Enzymatic Reaction Catalyzed by a Cyclin-Dependent Kinase"
Chem. Comm., 2003, 1308-1309. (Link)

1. F. Bernardi, A. Bottoni, M. De Vivo, M. Garavelli, G. Keserü, G. Náray-Szabó
"A Hypothetical Mechanism for HIV-1 Integrase Catalytic Action: DFT Modeling of a Bio-mimetic Environment"
Chem. Phys. Lett., 2002, 362, 1-7. (Link)



4. J. Dreyer, G. Brancato, E. Ippoliti, V. Genna, M. De Vivo, P. Carloni, U. Rothlisberger 
“First Principle Methods in Biology: From Continuum Models to Hybrid Ab Initio Quantum Mechanics/Molecular Mechanics”
in "Simulating Enzyme Reactivity"  - Published by The Royal Society of Chemistry
Edited by Iñaki Tuñón and Vicente Moliner, In press - Invited contribution

3. G. Palermo, M. De Vivo*
“Computational Chemistry for Drug Discovery"
Encyclopedia of Nanotechnology, Springer – 2015, pp 1-15 (Link) - Invited contribution

2. M. Cascella, M. Dal Peraro, M. De Vivo*
“Computational chemistry strategies tackling function and inhibition of pharmaceutically relevant targets”
Pp. 290-343 (54) in Volume 1 of the eBooks series entitled
“Frontiers in Computational Chemistry” by Bentham Science Publishers – 2015 (Link) - Invited contribution

1. A. Lodola and M. De Vivo*
“The increasing role of QM/MM in drug discovery”
in “Structural and mechanistic enzymology: Bringing together experiments and computing”,
Edited by Christo Z. Christov and Tatyana Karabencheva-Christova, Elsevier – 2012 (Link) - Invited contribution


"Enzyme Technologies: Pluripotent Players in Discovering Therapeutic Agents."
Edited by Hsiu-Chiung Yang, Wu-Kuang Yeh, James R. McCarthy  (Wiley)

Dr. Marco De Vivo


Volume 10, Issue 8, page 1443, August 2015 (Link) - Invited contribution




6. IT MI2014A000863
"Benzoxazolone derivatives as Acid Ceramidase inhibitors, and their use as medicaments"
Piomelli D., Pagliuca C., Pizzirani D., Bach A., Realini N., De Vivo M.

5. WO 2014/023643 A1
“Multitarget FAAH and COX inhibitors and therapeutical uses thereof”
De Vivo M., Scarpelli R., Cavalli A., Migliore M., Piomelli D., Habrant D., Favia A.D. 

4. PCT/EP2012/061662 
“Carprofen derivatives as inhibitors of FAAH and/or COXs”
De Vivo M., Scarpelli R., Cavalli A., Favia A.D., Habrant D., Piomelli D.


Joint inventor of 3 patents from Rib-X Pharmaceuticals (now, Melinta Therapeutics):

“Antimicrobial compounds and methods of making and using the same”These three International applications have entered national stages in tens of nations/regions worldwide and have already three US Patents granted:  

3. PCT/US10/52928 
Duffy E., Bhattacharjee A., O’Dowd H., De Vivo M., Du Y., Sinishtaj S., Tang Y., Wimberly B.

2. PCT/US10/052924
Duffy E., Bhattacharjee A., O’Dowd H., Chen S., De Vivo M., Lou R., Wimberly B.

1. PCT/US10/52922 
Duffy E., Bhattacharjee A., O’Dowd H., De Vivo M., Kanyo Z., Martinow J., Paik I., Scheideman M., Sinishtaj S., Wimberly B., Wu Y.


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I numeri di IIT

L’Istituto Italiano di Tecnologia (IIT) è una fondazione di diritto privato - cfr. determinazione Corte dei Conti 23/2015 “IIT è una fondazione da inquadrare fra gli organismi di diritto pubblico con la scelta di un modello di organizzazione di diritto privato per rispondere all’esigenza di assicurare procedure più snelle nella selezione non solo nell’ambito nazionale dei collaboratori, scienziati e ricercatori ”.

IIT è sotto la vigilanza del Ministero dell'Istruzione, dell'Università e della Ricerca e del Ministero dell'Economia e delle Finanze ed è stato istituito con la Legge 326/2003. La Fondazione ha l'obiettivo di promuovere l'eccellenza nella ricerca di base e in quella applicata e di favorire lo sviluppo del sistema economico nazionale. La costruzione dei laboratori iniziata nel 2006 si è conclusa nel 2009.

Lo staff complessivo di IIT conta circa 1440 persone. L’area scientifica è rappresentata da circa l’85% del personale. Il 45% dei ricercatori proviene dall’estero: di questi, il 29% è costituito da stranieri provenienti da oltre 50 Paesi e il 16% da italiani rientrati. Oggi il personale scientifico è composto da circa 60 principal investigators, circa 110 ricercatori e tecnologi di staff, circa 350 post doc, circa 500 studenti di dottorato e borsisti, circa 130 tecnici. Oltre 330 posti su 1400 creati su fondi esterni. Età media 34 anni. 41% donne / 59 % uomini.

Nel 2015 IIT ha ricevuto finanziamenti pubblici per circa 96 milioni di euro (80% del budget), conseguendo fondi esterni per 22 milioni di euro (20% budget) provenienti da 18 progetti europei17 finanziamenti da istituzioni nazionali e internazionali, circa 60 progetti industriali

La produzione di IIT ad oggi vanta circa 6990 pubblicazioni, oltre 130 finanziamenti Europei e 11 ERC, più di 350 domande di brevetto attive, oltre 12 start up costituite e altrettante in fase di lancio. Dal 2009 l’attività scientifica è stata ulteriormente rafforzata con la creazione di dieci centri di ricerca nel territorio nazionale (a Torino, Milano, Trento, Parma, Roma, Pisa, Napoli, Lecce, Ferrara) e internazionale (MIT ed Harvard negli USA) che, unitamente al Laboratorio Centrale di Genova, sviluppano i programmi di ricerca del piano scientifico 2015-2017.

IIT: the numbers

Istituto Italiano di Tecnologia (IIT) is a public research institute that adopts the organizational model of a private law foundation. IIT is overseen by Ministero dell'Istruzione, dell'Università e della Ricerca and Ministero dell'Economia e delle Finanze (the Italian Ministries of Education, Economy and Finance).  The Institute was set up according to Italian law 326/2003 with the objective of promoting excellence in basic and applied research andfostering Italy’s economic development. Construction of the Laboratories started in 2006 and finished in 2009.

IIT has an overall staff of about 1,440 people. The scientific staff covers about 85% of the total. Out of 45% of researchers coming from abroad 29% are foreigners coming from more than 50 countries and 16% are returned Italians. The scientific staff currently consists of approximately 60 Principal Investigators110 researchers and technologists350 post-docs and 500 PhD students and grant holders and 130 technicians. External funding has allowed the creation of more than 330 positions . The average age is 34 and the gender balance proportion  is 41% female against 59% male.

In 2015 IIT received 96 million euros in public funding (accounting for 80% of its budget) and obtained 22 million euros in external funding (accounting for 20% of its budget). External funding comes from 18 European Projects, other 17 national and international competitive projects and approximately 60 industrial projects.

So far IIT accounts for: about 6990 publications, more than 130 European grants and 11 ERC grants, more than 350 patents or patent applications12 up start-ups and as many  which are about to be launched. The Institute’s scientific activity has been further strengthened since 2009 with the establishment of 11 research nodes throughout Italy (Torino, Milano, Trento, Parma, Roma, Pisa, Napoli, Lecce, Ferrara) and abroad (MIT and Harvard University, USA), which, along with the Genoa-based Central Lab, implement the research programs included in the 2015-2017 Strategic Plan.