Mechanisms underlying sequence-independent beta-sheet formation

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Abstract
We investigate the formation of beta-sheet structures in proteins without taking into account specific sequence-dependent hydrophobic interactions. To accomplish this, we introduce a model which explicitly incorporates both solvation effects and the angular dependence (on the protein backbone) of hydrogen bond formation. The thermodynamics of this model is studied by comparing the restricted partition functions obtained by "unfreezing" successively larger segments of the native beta-sheet structure. Our results suggest that solvation dynamics together with the aforementioned angular dependence gives rise to a generic cooperativity in this class of systems; this result explains why pathological aggregates involving beta-sheet cores can form from many different proteins. Our work provides the foundation for the construction of phenomenological models to investigate the competition between native folding and non-specific aggregation.

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