%0 Book Section %1 statphys23_0820 %A Cecconi, F. %A Piazza, F. %A Rios, P. De Los %B Abstract Book of the XXIII IUPAP International Conference on Statistical Physics %C Genova, Italy %D 2007 %E Pietronero, Luciano %E Loreto, Vittorio %E Zapperi, Stefano %K binding dissociation kinetics pdz-domains proteins statphys23 topic-10 %T Unbinding of peptides from PDZ domains is diffusion-limited %U http://st23.statphys23.org/webservices/abstract/preview_pop.php?ID_PAPER=820 %X PDZ domains are typical examples of binding proteins forming protein-protein assemblies and suitably design for the binding. They bind other proteins by recognizing their carboxy-terminal motifs, and understanding the interplay of structure, chemistry and dynamics leading to the PDZ function represent a challenge in biomolecular sciences. In this paper we have characterized, via Molecular Dynamics simulations based on a coarse-grained description of PDZ domains, the influence of native state topology on the thermodynamics and the kinetics of the dissociation mechanism for a complex PDZ3-peptide. The native centric approach we have followed neglects chemical details but incorporates the minimal structural information to reproduce the protein dynamics which couples to binding and which is relevant to the function. We suggest that at physiological temperatures, close to the PDZ unfolding transition, the unbinding of a peptide from the PDZ domain becomes increasingly diffusive rather than thermally activated, resulting in a significant slow down of the process of up to two to three orders of magnitude with respect to the naive extrapolation from low temperature calculations.

@incollection{statphys23_0820, abstract = {PDZ domains are typical examples of binding proteins forming protein-protein assemblies and suitably design for the binding. They bind other proteins by recognizing their carboxy-terminal motifs, and understanding the interplay of structure, chemistry and dynamics leading to the PDZ function represent a challenge in biomolecular sciences. In this paper we have characterized, via Molecular Dynamics simulations based on a coarse-grained description of PDZ domains, the influence of native state topology on the thermodynamics and the kinetics of the dissociation mechanism for a complex PDZ3-peptide. The native centric approach we have followed neglects chemical details but incorporates the minimal structural information to reproduce the protein dynamics which couples to binding and which is relevant to the function. We suggest that at physiological temperatures, close to the PDZ unfolding transition, the unbinding of a peptide from the PDZ domain becomes increasingly diffusive rather than thermally activated, resulting in a significant slow down of the process of up to two to three orders of magnitude with respect to the naive extrapolation from low temperature calculations.}, added-at = {2007-06-20T10:16:09.000+0200}, address = {Genova, Italy}, author = {Cecconi, F. and Piazza, F. and Rios, P. De Los}, biburl = {https://www.bibsonomy.org/bibtex/208143a12951eb8df29635c7e4b2ae839/statphys23}, booktitle = {Abstract Book of the XXIII IUPAP International Conference on Statistical Physics}, editor = {Pietronero, Luciano and Loreto, Vittorio and Zapperi, Stefano}, interhash = {8b84f439eacb9ac840a64f3f60175f59}, intrahash = {08143a12951eb8df29635c7e4b2ae839}, keywords = {binding dissociation kinetics pdz-domains proteins statphys23 topic-10}, month = {9-13 July}, timestamp = {2007-06-20T10:16:30.000+0200}, title = {Unbinding of peptides from PDZ domains is diffusion-limited}, url = {http://st23.statphys23.org/webservices/abstract/preview_pop.php?ID_PAPER=820}, year = 2007 }