ATOMIC ENVIRONMENT ENERGIES IN PROTEINS DEFINED FROM STATISTICS OF ACCESSIBLE AND CONTACT SURFACE-AREAS

Atomic contact potentials are derived by statistical analysis of atomi c surface contact areas versus atom type in a database of non-homologo us protein structures. The atomic environment is characterized by the surface area accessible to solvent and the surface of contacts with po lar and non-polar atoms. Four types of atoms are considered, namely ne utral polar atoms from protein backbones and from protein side-chains, non-polar atoms and charged atoms. Potential energies Delta E(j)(E) a re defined from the preference for an atom of type j to be in a given environment E compared to the expected value if everything was random; Boltzmann's law is then used to transform these preferences into ener gies. These new potentials very clearly discriminate misfolded from co rrect structural models. The performance of these potentials are criti cally assessed by monitoring the recognition of the native fold among a large number of alternative structural folding types (the hide-and-s eek procedure), as well as by testing if the native sequence can be re covered from a large number of randomly shuffled sequences for a given 3D fold (a procedure similar to the inverse folding problem). We sugg est that these potentials reflect the atomic short range non-local int eractions in proteins. To characterise atomic solvation alone, similar potentials were derived as a function of the percentage of solvent-ac cessible area alone. These energies were found to agree reasonably wel l with the solvation formalism of Eisenberg and McLachlan.