How many fold types of protein are there in nature?

Many protein structures have now been determined and reveal that protein molecules can adopt the same fold despite having very different sequences. It has been suggested that, owing to different stereochemical constraints, the number of ways that a sequence can fold may be limited. Therefore, it is reasonable to ask how many fold types exist in nature. Several groups have tackled this problem with very different results. In the present study, a novel statistical sampling approach is used to reestimate this number. The results suggest that the number of protein folds in nature is probably several hundreds.