University of Cagliari
Structure, affinity and specificity riddles in biomolecular interactions
01 July 2015
Dipartimento di Fisica
Nell’ambito del programma Visiting Professor 2014-2015 finanziato dalla Regione Autonoma della Sardegna, il Prof.
Alexandre M.J.J. Bonvin (Utrecht University, the Netherlands)
terra’ il giorno 1 luglio, alle 11:30, nell’Aula A del Dipartimento di Fisica il seguente seminario:
Structure, affinity and specificity riddles in biomolecular interactions
Biomolecular interactions underlie most cellular processes, including signal transduction and apoptosis.
Understanding how the cell works requires describing these at molecular level, which is bound to have a
dramatic impact on current and future structure-based drug design. Integrative, computational structural
biology approaches [1] can assist in the task of generating 3D models of those macromolecular assemblies.
We have developed for this purpose an information-driven docking approach called HADDOCK
(http://bonvinlab.org/software). In my talk I will first introduce our integrative modelling approach HADDOCK.
I will then discuss the problem of binding affinity prediction, showing that current scoring functions in
macromolecular docking fail at predicting the affinity of protein-protein complexes and that additional
structural parameters, previously neglected are deemed mandatory for near-accurate predictions [2].
Related to affinity, understanding the structural determinant of specificity is another challenging problem, which
I will shortly illustrate showing how a conserved Asp to Glu mutation can switch the specificity profile of
ubiquitination enzymes [3].
[1] J.P.G.L.M Rodrigues and A.M.J.J. Bonvin. Integrative computational modeling of protein
interactions. FEBS J., 281, 1988-2003 (2014).
[2] P.L. Kastritis, J.P.G.L.M Rodrigues, G.E. Folkers, R. Boelens and A.M.J.J. Bonvin. Proteins
feel more than they see: Fine-tuning of binding affinity by properties of the non-interacting surface.
J. Mol. Biol. 426, 2632-2652 (2014).
[3] S.J.L. van Wijk, A.S.J. Melquiond, S.J. de Vries, H.Th.M Timmers and A.M.J.J. Bonvin. Dynamic
control of selectivity in E2-E3 interactions via a salt-bridge network revealed by an ASP to GLU substitution.
PLoS Comp. Biol., 8(11), e1002754 (2012).
Per ulteriori informazioni rivolgersi a paolo.ruggerone@dsf.unica.it