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.
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