Activities of the neutrally evolved P450s on the six substrates. The heat map shows the fold change in activity of all 34 neutrally evolved P450 variant on all six substrates. Each row shows the data for a different P450 variant, while each column shows the activity on a different substrate. The fold change in activity is the ratio of the variant's activity to that of the neutral evolution parent. Both the substrates and the P450 variants are hierarchically clustered according to the activity profiles, as shown by the dendrograms at top and left. Substrate abbreviations are the same as those used in the text: PROP – propranolol, 2A5C – 2-amino-5-chlorobenzoxazole, MDOB – 1,2-methylenedioxybenzene, 2PE – 2-phenoxyethanol, 11PA – 11-phenoxyundecanoic acid. The standard errors for the changes in activity displayed in the heat map tend to be much smaller than the changes themselves; these errors are shown explicitly in Figure 3.