SynopsisA three-dimensional lattice model of protein designed to assimilate lysozyme is introduced. An attractive interaction is assumed to work between preassigned specific pairs of units, when they occupy the nearest-neighbor lattice points. The behavior of this lattice lysozyme is studied by a Monte Carlo simulation method. Because of the specific interunit interactions, "native state" of the lattice lysozyme is stable at low temperatures. Conformational fluctuations in the native state are observed to occur a t both termini and loop regions of the main chain existing on the surface. The process of unfolding and the denatured states of this model are discussed. Complete refolding from a denatured state was not observed. However, by starting from partially folded structures, the native conformation could be attained. From these observations it is concluded that, in the process of folding of proteins as simplified in a lattice model, nucleation is a rate-limiting factor. The artificial character of this model and possible improvement are discussed.

A lattice model of proteins is introduced. “A protein molecule” is a chain of non‐intersecting units of a given length on the two‐dimensional square lattice. The copolymeric character of protein molecules is incorporated into the model in the form of specificities of inter‐unit interactions. This model proved most effective for studying the statistical mechanical characteristics of protein folding, unfolding and fluctuations. The specificities of inter‐unit interactions are shown to be the primary factors responsible for the all‐or‐none type transition from native to denatured states of globular proteins. The model has been studied by the Monte Carlo method of Metropolis et al., which is now shown applied to approximately simulating a kinetic process. In the strong limit of the specificity of the inter‐unit interaction the native conformation was reached in this method by starting from an extended conformation. The possible generalization and application of this method for finding the native conformation of proteins from their amino acid sequence are discussed.

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A theory is developed about large‐amplitude conformational fluctuations in globular proteins in their native or predenaturational state. A model is introduced, an independent fluctuating site model, in which we assume that there is more than one independent fluctuating site, each one localized in some part of a protein molecule. Without assuming any further details for each fluctuating site, the entropy S versus enthalpy H curve of this model is shown to be convex. From this fact the predenaturational excess heat capacity can be derived, as observed in recent experimental studies of a few systems of a protein in solution.