Dynamics-based alignment: a novel tool for comparing large-scale movements in proteins with same or different fold

by Dr Andrea Zen (SISSA, Trieste)

Thursday 30 Apr 2009, 17:00 → 18:00 Europe/Rome

Aula Conversi (Dipartimento di Fisica - Ed. G. Marconi)

The biological function of several proteins and enzymes is assisted by large-scale conformational changes that are excited in thermal equilibrium. Following the logical cascade: sequence -> structure -> function, it is expected that the functional movements of a protein are influenced by the structural architecture. Proteins with similar structures are known to sustain similar large-scale movements; yet it has recently emerged that similar functional movements are shared by proteins with different architecture or topology [Carnevale et al. JACS 2006, Capozzi et al. J_Proteome_Res 2007, Zen et al. Prot_Sci 2008]. The availability of quantitative methods for comparing the functional-oriented dynamics in proteins would allow to take to a new level the investigation of the structure/function relationship. We report on a first attempt in this direction by discussing a pairwise alignment scheme that identifies groups of amino acids that undergo similar concerted movements in proteins. The alignment method is based on a coarse-grained elastic network model and requires as input the sole proteins' native structures. We present two applications of this alignment: a comparison of a dataset of >70 enzymes covering the main functional and structural classes, and a method to predict nucleic-acid-binding sites in proteins.