Reads meet rotamers: structural biology in the age of deep sequencing

Structure has traditionally been interrelated with sequence, usually in the framework of comparing sequences across species sharing a common fold. However, the nature of information within the sequence and structure databases is evolving, changing the type of comparisons possible. In particular, we now have a vast amount of personal genome sequences from human populations and a greater fraction of new structures contain interacting proteins within large complexes. Consequently, we have to recast our conception of sequence conservation and its relation to structure - for example, focusing more on selection within the human population. Moreover, within structural biology there is less emphasis on the discovery of novel folds and more on relating structures to networks of protein interactions. We cover this changing mindset here.