About 200 mRNA sequences of Escherichia coli and human with matching protein secondary structure delta. were studied. The m RNA folding for each native sequence and for corresponding randomized sequences was calculated through free energy minimization. We have found that the folding energy of mRNA segments in different protein secondary structures is significantly different. The average Z score is more negative for regular secondary structure (alpha-helix and beta-strand) than that for coil. This suggests that the codon choice in native mRNA sequence coding for protein regular structure contributes more to the mRNA folding stability. (c) 2006 Elsevier Inc. All rights reserved.