Analysis of chameleon sequences by energy decomposition on a pairwise per-residue basis

초록

The conversion from alpha-helix to beta-strand that has been widely observed in so-called chameleon sequences has received considerable attention since such a structural change may induce many amyloidogenic proteins to self-assemble into fibrils thus causing fatal diseases. Here we report a large scale-analysis of the energetics of secondary structural conversions in a collection of chameleon sequences retrieved from the Protein Data Bank. Major energetic contributions to the secondary structural conversion were analyzed by carrying out energy decomposition on a pairwise per-residue basis, i. e., ( i, i), ( i, i +/- 1), ( i, i +/- 2), ( i, i +/- 3), ( i, i +/- 4) and > ( i, i +/- 4) intra-/inter-residual interactions. While the overall potential energy differences were subtle, individual residue-based interacting energy differences were observed to vary significantly depending on the specific type of secondary structural conversion. The average energy difference between alpha-helix and beta-strand, < Delta E-alpha ->beta >, in the chameleon sequences varied significantly in ( i, i), ( i, i +/- 1) and > ( i, i +/- 4) interactions. The major energetic factors in secondary structure conversions were electrostatic interactions and the polar term for solvation energy. In addition, residue-based average energy differences in alpha-helix -> beta-strand conversions were well-correlated to those in alpha-helix -> random coil -> beta-strand conversions ( R-2 = 0.92). Assuming that three secondary structural elements can transform in either direction, this strong correlation indicates that the present energy decomposition method using database structures of chameleon sequences provides a reliable tool for the characterization of secondary structure fluctuations in amino acid sequences.

키워드