Biomolecular Simulations Laboratory

>>Biomolecular Simulations Laboratory

Biomolecular simulations make use of computer programs to recreate and visualize the behavior and phenomena that rule biological processes at the molecular level. These tools make it possible to simulate experiments in more controlled conditions than in cells or living organisms, and to perform “theoretical experiments” that would be technically impossible.

These possibilities have resulted in important advances in biomedicine, facilitating the understanding of mechanisms of diseases and the development of drugs, for example.

In the Biomolecular Simulations Laboratory, we apply different molecular modelling techniques and simulations to several problems of biomedical interest, such as the stability of viral particles of Zika and Dengue or interactions between proteins that participate in the contraction of the cardiac muscle. These activities are carried out in collaboration with experimental groups in Uruguay and abroad.

Finally, an important part of our work is dedicated to the development of coarse-grained methods to perform advanced simulations at low computational cost. These methods offer the possibility of improving the comparability of theoretical studies with biochemical / biophysical or molecular biology experiments.


Matías Machado, PhD
Associate researcher

Leonardo Darré, PhD

External collaborator

Exequiel Barrera, PhD

IP Montevideo Postdoc

Pablo Garay, PhD

CONICET Postdoc

Florencia Klein, BSc

Postgraduate student

Martín Sóñora, MSc

PhD Student
  • Development of the SIRAH coarse-grained force field (Southamerican Initiative for a Rapid and Accurate Hamiltonian).
    Our group develops and maintains one of the broadest coarse-grained force fields for existing biomolecular simulations. SIRAH (www.sirahff.com) uses a Top Down approach and a classic Hamiltonian, common to atomic force fields. SIRAH is freely distributed with easy-to-use analysis tools, parameters and topologies to simulate DNA, proteins, explicit solvent and phospholipids. Currently, representations are being developed for metal ions, glycans and RNA. This line is entirely developed by our group.

  • Development of FRET sensors for cyclic nucleotide and redox signalling pathways.
    Using bioinformatics and structural modelling, together with coarse-grained simulations, we have developed a new generation of FRET sensors for signaling cAMP, cGMP and redox conditions. These biosensors allow us to reach an unprecedented spatial resolution since they can be genetically fused to the C-terminal of virtually any protein, directing them to any cell compartment. This research line continues with the design of new generations of biosensors in the framework of the ProTeMCA program and in collaboration with foreign experimental groups.

  • Flavivirus stability studies.
    Using multiscale simulations, we study the different factors that affect the stability of viral particles (Virus-like Particles). The reduced computational cost of our simulation scheme allows us to perform comparative simulations of different flaviviruses varying the temperature and pH conditions. The availability of experimental structures of viral particles of Zika, Dengue, Japanese encephalitis (JEV) and tick-borne Encephalitis virus (TBEV) allows us to study the accessibility of different epitopes, helping to understand the mechanisms of viral neutralization by antibodies. Additionally, the computational approach enables the identification of amino acids involved in the acid firing mechanism of flaviviruses, which could contribute significantly to the development of vaccines through the creation of attenuated viruses. These studies are part of collaborations with national and foreign experimental groups.

  • “Latin American Initiative for Molecular Simulations”. Expert´s meeting. Nov. 2018. IP Montevideo.

  • OpenLab “Performing Molecular Simulations with the Sirah force field”. 2015 and 2017 editions. IP Montevideo. Organizer: Sergio Pantano.

  • VIII PostLATAM course Membrane Lipids, Transporters, Channels…and all that crosstalk, Nov. 2015, Salto, Uruguay.

  • Joint meeing SAB/SBFUy “Latin American Crosstalk in Biophysics and Physiology”, November 2015, Salto, Uruguay.

  • “Introduction to Structural Biology and Bioinformatics”, November 2013. IP Montevideo.

  • Course and workshop “Ion Channels: From Molecules to Pathology”, April 2012. Universidad de la República – IP Montevideo.

  • Course “NFS Workshop on Multiscale Modeling and Simulation”, September 2012, IP Montevideo.

  • “Hands-on Course: Coarse Grain Methods for Biomolecular Simulations”, September 2011, IP Montevideo.

  • Course and workshop “Computational Modelling and Simulation of Biological Systems”, February 2010, IP Montevideo.

  • “Conference on Molecular Aspects of Cell Biology: A Perspective from Computational Physics”, October 2010. International Centre for Theoretical Physics (ICTP), Trieste, Italia

  • 2018-2019 – “Modulation of G-protein coupled receptors through molecular dynamics simulations as a tool for the rational planning of new drugs”. Responsible: Hugo Verli-Sergio Pantano. LNCC, Santos Dumont, Brazil.

  • 2017-2018 – “In silico characterization of drug targets for Zika and Dengue”. Responsible: Gustavo Seabra-Sergio Pantano. LNCC, Santos Dumont, Brazil.

  • 2018-2020 – “Molecular mechanism of signaling in bacteria: directionality from signal to response”. Responsible: Alejandro Buschiazzo. Clemente Estable Fund, ANII.

  • 2015-2018 – “Design of biosensors for simultaneous monitoring of redox signaling and cAMP: From the computer to the cell and back to the computer”. Responsible: Sergio Pantano. María Viñas Fund, ANII

  • Tosar JP, Gambaro F, Darré L, Westhof E, Cayota A, Dimerization confers increased stability to nucleases inextracellular 5’ halves from glycine and glutamic acid tRNAs. NAR, In press. DOI: 10.1093/nar/gky495

  • Zonta F, Buratto D, Crispino G, Carrer A, Bruno F, Yang G, Mammano F and Pantano S. Cues to opening mechanisms from in silico electric field excitation of Cx26 hemichannel and in vitro mutagenesis studies in HeLa transfectans. Frontiers in Molecular Neuroscience. 2018, vol 11, art 170.

  • Esteban C, Donati I, Pantano S, Villegas M, Benegas J, Paoletti S, Dissecting the conformational determinants of Chitosan and Chitlac oligomers. Biopolymers, 2018, e23221.

  • Viso JF, Belelli P, Machado M, González H, Pantano S, Amundarain MJ, et al. (2018) Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly. PLoS Comput Biol 2018, 14(4): e1006082.

  • Sulpizi M, Faller R, Pantano S. Multiscale modeling on biological systems. BBRC. 2018, 498:263.

  • Brandner AF, Schueller A, Melo F, Pantano S. Exploring DNA dynamics within oligonucleosomes with coarse-grained simulations: SIRAH force field extension for protein-DNA complexes. BBRC, 2018, 498:319

  • Machado M, Gonzalez HC, Pantano S. MD Simulations of Virus-Like Particles with Supra CG solvation affordable to desktop computers. JCTC. 2017, 13: 5106.

  • Marcello A, Pantano S. Interdisciplinary approaches to the study of flavivirus. BBRC, 2017, 492:531.

  • Barrera E, Frigini EN, Porasso RD, Pantano S. Modeling DMPC lipid membranes with SIRAH force-field. Journal of Molecular Modelling. 2017, 23: 259

  • Surdo N, Berrera M, Koschinski A, Brescia M, Machado M, Carr C, Morotti S, Grandi E, Wright P, Bers D, Gorelik J, Pantano S, Zaccolo M. FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility. Nature Comm, 2017, 8: 15031.

  • Festari MF,Trajtenberg F, Berois N, PantanoS , Revoredo L, Kong Y, et al. Revisiting the human polypeptide GalNAc-T1 and T13 paralogs. Glycobiology. 2017, 27:140.

  • Astrada S, Gomez Y, Obal G, Pritsch O, Vallespí MG, Bollati-Fogolín M. Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552. J. Pep. Sci. 2016, 22:711.

  • Calì T, Frizzarin M, Luoni L, Zonta F, Pantano S, Cruz C, Bonza MC, Bertipaglia I, Ruzzene, De Michelis MI, Damiano N, Marina O, Zanni G, Zanotti G, Brini M, Lopreiato R, Carafoli E. The ataxia related G1107D mutation of the plasma membrane Ca2 + ATPase isoform 3 affects its interplay with calmodulin and the autoinhibition process. BBA – Mol. Basis Dis. 2016, 1863:165.

  • Machado MR and Pantano S. SIRAH Tools: mapping, backmapping and visualization of coarse-grained models. Bioinformatics, 2016, 32:1568.

  • Machado MR and Pantano S. Exploring LacI−DNA Dynamics by Multiscale Simulations Using the SIRAH force field. JCTC, 2015, 11:5012.

  • Jäger AV, De Gaudenzi JG, Mild JG, Cormack BM, Pantano S, Altschuler DL, Edreira MM. Identification of novel cyclic nucleotide binding proteins in Trypanosoma cruzi. Mol Biochem Parasitol. 2015, 198:104.

  • Darré L, Machado MR, Brandner AF, Ferreira S, Gonzalez HC, Pantano S. SIRAH: a structurally unbiased coarse-grained force field for proteins with aqueous solvation and long-range electrostatics. JCTC, 2015, 11:723.

  • Morande PE, Borge M, Abreu C, Galletti J, Zanetti SR, Nannini P, Bezares RF, Pantano S, Dighiero G, Oppezzo P, Gamberale R, Giordano M. Surface localization of high-mobility group nucleosome-binding protein 2 (HMGN2) on leukemic B cells from chronic lymphocytic leukemia patients is related to secondary autoimmune hemolytic anemia. Leuk Lymphoma. 2015. Jan 21:1-8.

  • Sanguinetti M, Amillis S, Pantano S, Scazzocchio C and Ramón A. Modeling and mutational analysis of Aspergillus nidulans UreA, a member of the subfamily of urea/H+ transporters in fungi and plants. Open Biology, 2014, 4:140070

  • Zecchin A, Pattarini L, Gutierrez MI, Mano M, Mai A, Valente S, Myers MP, Pantano S, and Giacca M. Reversible acetylation regulates vascular endothelial growth factor receptor-2 activity. Journal of Molecular Cell Biology, 2014, 6:116.

  • Gonzalez HC, Darré, L. Pantano, S. Transferable Mixing of Atomistic and Coarse-Grain Water Models. J. Phys. Chem. B, 2013, 117 :14438.

  • Pantano S, Montecucco C. The Blockade of the Neurotransmitter Release Apparatus by Botulinum Neurotoxins. Cell. Mol. Life Sci. 2013, DOI:10.1007/s00018-013-1380-7.

  • Megighian A, Zordan M, Pantano S, Scorzeto M, Rigoni M, Zanini D, Rossetto O, Montecucco C. Evidence for a radial SNARE super-complex mediating neurotransmitter release at the Drosophila neuromuscular junction. J. Cell. Sci., 2013, 136: 3134.

  • Almeida RS, Loss O, Colabardini AC, Brown NA, Bignell E, Savoldi M, Pantano S, Goldman MH, Arst HN Jr, Goldman GH. Genetic Bypass of Aspergillus nidulans crzA Function in Calcium Homeostasis. G3 (Bethesda), 2013, 3:1129.