Deriving amino acid contact potentials from their frequencies of occurrence in proteins : a lattice model study

The possibility of deriving the contact potentials between amino acids from their frequencies of occurrence in proteins is discussed in evolutionary terms. This approach allows the use of traditional thermodynamics to describe such frequencies and, consequently, to develop a strategy to include in the calculations correlations due to the spatial proximity of the amino acids and to their overall tendency of being conserved in proteins. Making use of a lattice model to describe protein chains and defining a 'true' potential, we test these strategies by selecting a database of folding model sequences, deriving the contact potentials from such sequences and comparing them with the 'true' potential. Taking into account correlations allows for a markedly better prediction of the interaction potentials.