Protein folding mechanisms lattice models

C2.5.3.4 EXPLORING THE PROTEIN FOLDING MECHANISM USING THE LATTICE MODEL... 

Thirumalai, D., and Klimov, D. K. (1999). Deciphering the timescales and mechanisms of protein folding using minimal off-lattice models. Curr. Opin. Struct. Biol. 9, 197-207. 

Domain coalescence (Karplus and Weaver, 1976) is a possible mechanism for protein folding. Zientara et al. (1980) examined the dependence of the coalescence lifetime on the hydration shell. The lifetime depends on the activation barrier contributed by the shell and the extent of the shell. If domains resemble the native protein in hydration, then the minimal extent of the shell and its fluidity favor coalescence. In passing, one notes that the percolation model may apply to folding the coalescence of domains should be analogous to gelation or to diffusion on a partially filled lattice. 

D. Thirumalai, D. K. Klimov, and M. R. Betancourt, Exploring the folding mechanisms using lattice models, in Monte Carlo Approach to Biopolymers and Protein Folding, P. Giassbeiger, G. T. Barkema, and W. Nadler, eds., Singapore, World Scientific, 1998, pp. 19-28. 

Lau and Dill have also investigated the statistical mechanics of folding for simplified protein models on two-dimensional square lattices. They explored both conformational space (the set of all possible conformations) and sequence space (the set of all possible sequences) and concluded that many sequences have stable, compact, native-like structures. Another conclusion of these studies was that sequences tended to form a single, unique structure, even with only two types of residues (hydrophobic and polar). This tendency increased with chain length. Moreover, one or two mutations in these sequences did not greatly destabilize most folded states. 

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