Wednesday, 17th January 2018


Cell Biology and Immunology
               Bioinformatics Unit






Ugo Bastolla







Research summary:

  -----  Fig01-300


Disordered regions are abundant in protein complexes such as the Centrosome. Their evolution through large insertions is accelerated along branches in which the complexity of the organism increased more.



  Composite view depicting our interests and accomplishments in docking and scoring.

1) Stability, dynamics and evolution of proteins. Our group develops mathematical models for predicting protein folding stability, the effect of mutations, stability against misfolding and the corresponding selective pressures. We apply these models to simulate protein evolution and the effect of the evolutionary process (mutation rate, mutation bias, population size) on protein stability. Our torsional network model (TNM) allows simulating the equilibrium dynamics of proteins, characterizing allosteric and catalytic sites, and telling functional movements from conformation changes in response to a random perturbation. Within the TNM, we are developing an energy function to predict conformation changes and energy barriers. We study the evolution of disordered protein regions and their contribution to organism complexity.

2) Theoretical ecology and bacterial networks. We investigate the factors that influence ecosystem diversity, in particular competition and mutualism. By analyzing co-occurrences of bacteria in environmental samples, we predict their interaction networks and we proposed that mutualistic interactions favor bacterial cosmopolitanism and biodiversity.

3) Next generation sequencing. We developed the algorithm ZPeaks to detect peaks in sequencing experiments, and we applied it to the analysis of replication origins.

4) Drug design (line directed by Antonio Morreale). We completed a new version of our automatic platform for virtual screening VSDMIP, which allows finding candidate drugs based on the structure of the target protein or of known ligands, exploiting the graphical interface of the program PyMOL. We improved our docking algorithm and our scoring function, and we explored a new approach to drug design. Our new web application AtlasCBS allows mapping the chemical-biological space of drug design. Our experience with molecular modeling produced several collaborations, within as well as outside the CBMSO, and a patent application.


Relevant publications:

  • Bastolla, U., Bruscolini, P., and Velasco, J.L. (2012) Sequence determinants of protein folding rates: Positive correlation between contact energy and contact range indicates selection for fast folding. Proteins 80:2287-2304.
  • Liberles, D.A., et al. (2012) The interface of protein structure, protein biophysics and molecular evolution. Protein Sci. 21:769-785.
  • Nido, G.S., Méndez, R., Pascual-García, A., Abia, D. and Bastolla, U. (2012) Protein disorder in the centrosome correlates with complexity in cell types number. Mol. BioSystems, 8:353-367.
  • Bastolla, U. and Porto, M. (2012) Modeling structural and genomic constraints in the evolution of proteins. In: Dokholyan, N. (ed) Computational Modeling of Biological Systems: From Molecules to Pathways. Springer Verlag, New York, U.S.A.
  • Maalej, E., Chabchoub, F., Samadi, A., de los Ríos, C., Perona, A., Morreale, A., and Marco-Contelles, J. (2011) Synthesis, biological assessment and molecular modeling of 14-aryl-10,11,12,14-tetrahydro-9H-benzo[5,6]chromeno[2,3-b]quinolin-13-amines. Bioorg. Med. Chem. Lett. 21, 2384-2388.


Other activities:

- Organización del congreso “The emerging dynamics view of proteins: Protein plasticity in allostery, evolution and self-assembly”, Dresden, Germany, julio 2012, organizadores: U. Bastolla, M. Porto and H.E. Roman.

- Editor del número especial de la revista Biophysica and Biochimica Acta (Elsevier) dedicada al congreso “The emerging dynamics view of proteins” (U. Bastolla)

- Editor de la revista Peer J. (U. Bastolla)

- Comité científico de las Jornadas de Bioinformática 2012 (U. Bastolla, A. Morreale)

- Coordinador del curso de bioinformática del Master de Biofísica UAM (A. Pascual-García). Clases de bioinformática en el master de biofísica UAM (D. Abia, U. Bastolla, A. Cortés, J. Klett, R. Méndez, A. Morreale, A. Pascual-García), seminario en el master de bioinformática UCM (U. Bastolla)

- Curso 2011-2012 de Sistemas Biológicos en el grado de Ingeniería Biomédica de la Universidad Carlos III de Madrid (U. Bastolla).

- Solicitud de patente: F. Mayor-Menéndez, C. Murga-Montesinos, P.M. Campos-Muelas, J.J. Heijnen, A.M. Agnes, A. Kavelaars, A. Morreale y R. Gil. Nuevos compuestos inhibidores de p38MAPK y sus aplicaciones. N. de solicitud P201131754, 2 de noviembre de 2011. Propietario: UAM.

- Organización del taller práctico “Docking y cribado virtual: uso de herramientas computacionales en el diseño de fármacos”. 20-22 de junio de 2011, Madrid (A. Morreale)

- Presentaciones orales en congresos:

- U. Bastolla, Characterization of conformation changes in proteins with the torsional network model. Workshop “Allosteric Regulation of Cell Signalling”, CNIO, Madrid,17-19 September 2012.

- U. Bastolla, Modeling the mutual influence between folding and evolution. Workshop: Modeling protein structural and energetic constraints on sequence evolution. Durham, USA, Nov. 2011

- U. Bastolla, Contact interactions in proteins: Simple models give analytic insights on protein stability, evolution, and dynamics. Barcelona Supercomputing Center, Dec. 2011

- A. Pascual-García, Detecting bacterial interactions from environmental samples: Ecological aggregations favor bacterial cosmopolitanism. Jornadas de Bioinformática 2012, Barcelona.

- A. Morreale, A reverse combination of structure-based and ligand-based strategies for virtual screening. Jornadas de Bioinformática 2012, Barcelona.