ARE PROTEINS IDEAL MIXTURES OF AMINO-ACIDS - ANALYSIS OF ENERGY PARAMETER SETS

Various existing derivations of the effective potentials of mean force for the two-body interactions between amino acid side chains in prote ins are reviewed and compared to each other. The differences between d ifferent parameter sets can be traced to the reference state used to d efine the zero of energy. Depending on the reference state, the transf er free energy or other pseudo-one-body contributions can be present t o various extents in two-body parameter sets. It is, however, possible to compare various derivations directly by concentrating on the ''exc ess'' energy-a term that describes the difference between a:real prote in and an ideal solution of amino acids. Furthermore, the number of pr otein structures available for analysis allows one to check the consis tency of the derivation and the errors by comparing parameters derived from various subsets of the whole database. It is shown that pair int eraction preferences are very consistent throughout the database. Inde pendently derived parameter sets have correlation coefficients on the order of 0.8, with the mean difference between equivalent entries of 0 .1kT. Also, the low-quality (low resolution, little or no refinement) structures show similar regularities. There are, however, large differ ences between interaction parameters derived on the basis of crystallo graphic structures and structures obtained by the NMR refinement. The origin of the latter difference is not yet understood.