Effect of simulated neutral sequence drift on MFEDs of viruses with predicted RNA structure. Coding regions of complete genome sequences of HCV genotype 1b (GenBank accession number HPCJ491), HGV/GBV-B (genotype 2; HGU94695), and FMDV (PIFMDV2) were each mutated independently 10 times to produce sequences showing a range of sequence divergence from the original (X-axis). MFEDs, using the NDR algorithm to generate 50 sequence order randomized sequences, were calculated for each and expressed as a percentage of the MFED of the starting sequence (Y-axis). The distributions of MFED values for the mutated sequences are represented as box and whisker plots (showing 95% percentile [line], standard deviation [upper and lower box], and mean values [line within box], with outliers indicated by the symbol *). For comparison, MFEDs for naturally occurring variants in each virus group expressed as a percentage of the MFED of the starting sequences were plotted using the symbol •.