XXXV Reunião Anual da SBBqResumoID:9078


Effect of hydrogen bonds on homopolymeric collapse in a simple lattice model: Implications for protein folding cooperativity.


Fleury, G. M. N.1; Barbosa, M. A. A.2; Pereira de Araujo, A. F.3



1Inst. de Física, UnB, DF; 2Inst. de Física, USP, SP; 3Depto. de Biol. Celular, IB, UnB, DF

    Hydrogen bonds were previously included in a hydrophobic, two-dimentional protein lattice model by restricting the set of energetically relevant contacts of the system: only contacts between monomers possessing a local structure consistent with the formation of a hydrogen bond contributed to the energy. Such restriction corresponds to an effective reduction in lattice coordination of the model, since a subset of zh local conformations are favored within  a group of z possible local states. By applying this physically motived mechanism to different model proteins we observed, throuth Monte Carlo simulations, a large increase on the folding cooperativity parameter k, which is intended to correspond to the ratio between the van't Hoff and calorimetric enthalpies, and the expected increase in the convexity of the underlying microcanonical entropy as a function of energy.
    In the present work we investigate the effect of this hydrogen bond restriction in homopolymers in order to determine to what extent the previously observed increase in cooperativity depends on the heteropolymeric nature of the protein model or if it arises from a homopolymeric-like hydrophobic collapse. We consider short chain homopolymers and study them by means of complete enumeration of conformations and through a mean field analytical approach based on Flory's theory of excluded volume. Complete enumeration results show that k tends to limiting values as the number of monomers increases. For a fixed coordination number, we generally observe an improvement on cooperativity as the hydrogen bond criterion becomes more and more restrictive, until a certain maximum restriction is reached. The analytical description of the homopolymer collapse displayed the right cooperativity behavior when the coordination lattice is equal to z=3 and N=26 monomers and further studies are beeing performed for other coordination values.
    Our results suggest that hydrogen bonds can be partially responsible for the cooperativity observed in the folding of small two-state proteins and also that the compaction pre-folding transition, observed in some proteins, is likely to be more cooperative than usually assumed.