Amino acid propensities are position-dependent throughout the length of α-helices

The 20 commonly occurring amino acids have been shown to have distinct position-dependent, helix-forming propensities near the ends of alpha-helices. Here, we show that the amino acids also have very strong position-dependent propensities throughout the length of a helix. Most helices are amphiphilic, and they have a strong tendency to both begin and end on the solvent-inaccessible face of the helix. These position-specific propensities should provide valuable parameters to guide de novo protein design, and should allow more precise prediction of helical topology in natural proteins. (C) 2004 Elsevier Ltd. All rights reserved.