Medium- and long-range interaction parameters between amino acids for predicting three-dimensional structures of proteins.
In a previous paper, a hypothesis for protein folding was proposed in which the native structure is formed by a three-step mechanism: (A) formation of ordered backbone structures by short-range interactions, (B) formation of small contact regions by medium-range interactions, and (C) association of the small contact regions into the native structure by long-range interactions. In this paper the empirical interaction parameters, used as a measure of the medium- and long-range interactions (the standard free energy, deltaGdegrees k,l, of formation of a contact between amino acids of species k and l) that include the role of the solvent (water) and determine the conformation of a protein in steps B and C, are evaluated from the frequency of contacts in the x-ray structures of native proteins. The numerical values of deltaG degrees k,l for all possible pairs of the 20 naturally occurring amino acids are presented. Contacts between highly nonpolar side chains of amino acids such as Ile, Phe, Trp, and Leu are shown quantitatively to be stable. On the contrary, contacts involving polar side chains of amino acids such as Ser, Asp, Lys, and Glu are significantly less stable. While this implies, in a quantitative manner, that it is generally more favorable for nonpolar groups to lie in the interior of the protein molecule and for the polar side chains to be exposed to the solvent (water) rather than to form contacts with other amino acids, many exceptions to this generalization are observed.
D000596:Amino Acids; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D011487:Protein Conformation; D013816:Thermodynamics
D000596:Amino Acids