Correspondence of potentials of mean force in proteins and in liquids

The concept of potential of mean force (PMF) is now widely used in predicti ng protein structures. Proteins notably differ from liquids by their inhomo geneity and chain connectivity. Does meaningful correspondence exist betwee n PMFs in proteins and PMFs in liquids? This question was addressed in this article. We constructed "proteins" each with 90 residues selected from a s ystem of 500 hard spheres. The residues were of two types, N and P. They in teract among themselves (with energies E-NN, E-PP, E-NP) and the 410 "solve nt" spheres (with energies E-NS and E-PS). Out of the 500 hard spheres, we first identified all chains consisting of 90 residues that have appropriate distances between nearest neighbors. The conformation of a protein was sel ected as the one having the lowest total energy among the 3.7 million chain s. A corresponding liquid system was constructed without imposing distance constraints among solute spheres. The PMFs obtained from the proteins and t he liquid system show remarkable similarities. For eleven sets of the energ y parameters, the first minima of the PMFs in the proteins agree with their counterparts in the liquid state to within a constant. (C) 2000 American I nstitute of Physics. [S0021-9606(00)51235-5].