Scientific Calendar Event



Starts 30 Nov 2010 11:30
Ends 30 Nov 2010 20:00
Central European Time
ICTP
Leonardo da Vinci Building Luigi Stasi Seminar Room
Strada Costiera, 11 I - 34151 Trieste (Italy)
The structure of proteins puts constraints on the evolution of their sequence. A random mutation of a residue in a protein (or an interacting protein pair) may lead to conflicts with the chemical and physical properties of its directly neighboring residues in the folded protein (or the assembled protein complex) and decrease the stability of the protein (or protein complex). As a consequence, correlations in the amino-acid occupation of residues in contact emerge in the course of evolution. Seen the huge increase in sequenced genomes, I will discuss the inverse problem: Given large multiple-sequence alignments of evolutionarily related (homologous) proteins, can we identify residue contacts by statistical analysis of amino acid frequencies? A maximum-entropy approach leads directly to the inverse Potts problem, i.e., to the inference of the coupling strengths of a disordered Potts model from a set of given equilibrium configurations. I will formulate several approaches to solve this problem (Boltzmann learning, mean field, TAP, susceptibility propagation), and I will show that statistical-physics based approaches lead to a huge increase in prediction power compared to more traditional correlation analysis, even if unexpected differences between the various methods emerge. I will also show that the identified contacts enable us to perform structural predictions of protein complexes, and shed light on the interaction specificity in bacterial signal transduction.
  • M. Poropat