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BP: Fachverband Biologische Physik
BP 25: Statistical Physics in Biological Systems III (joint DY, BP)
BP 25.4: Talk
Thursday, March 17, 2011, 11:15–11:30, ZEU 260
Negative design in protein folding: The role of correlations — •Jonas Minning1, Ugo Bastolla2, and Markus Porto3 — 1Institut für Festkörperphysik, Technische Universität Darmstadt, Germany — 2Centro di Biología Molecular ‘Severo Ochoa’, Madrid, Spain — 3Institut für Theoretische Physik, Universität zu Köln, Germany
Assessing the stability of a protein sequence folded into its native structure is a crucial aspect of protein design and of understanding protein evolution. Folding stability has two sides: (i) stability against the unfolded ensemble, which is usually achieved by evolution providing the native state with native contacts that are attractive enough to compensate for the loss of conformational entropy (positive design), and (ii) stability against incorrectly folded (misfolded) structures with low free energy, which is achieved through negative design.
A simple approximation based on the Random Energy Model (REM) and hence on the neglect of correlations predicts that negative design can be achieved by reducing the variance of the contact interaction energies of all possible residue-residue contacts. We verify that this approximation provides a good fit of the minimum free energy of misfolded structures. Nevertheless, our results suggest that negative design in protein evolution follows actually a completely different strategy, namely utilizing structural correlations between pairs of positions in the misfolded ensemble, which are neglected in the REM approach. We discuss how the REM approach might be generalized to include these correlations.