Folding Properties in Off-Lattice Protein Models

The thermodynamic behavior of an oo-lattice model for protein folding is probed in two and three dimensions. The model has only two types of residues, hydrophobic and hydrophilic. Our ability to map out the thermodynamics of the oo-lattice models relies heavily upon the eeciency of the simulated tempering algorithm. In this approach, the temperature is a uctuating variable, enabling the crossing of free energy barriers. In absence of local interactions, native structure formation does not occur in 3D. By including sequence independent local interactions, which qualitatively reproduce local properties of real proteins, the dominance of a native state for many sequences is observed. As in lattice model approaches, folding takes place by gradual compactiication, followed by a sequence dependent folding transition. In contrast to earlier studies using lattice models, our results convincingly demonstrate that one does not need more than two types of residues to generate sequences with good thermodynamic folding properties in 3D. A statistical analysis of hydrophobicity patterns is performed. Deviations from randomness are found for real proteins. The same type of deviations from randomness are found for good-folding sequences in 2D. An interpretation of the deviations is given in terms of an Ising model.