title: Reads meet rotamers: structural biology in the age of deep sequencing.
abstract: 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.
authors.affiliation: Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, United States.
authors.forename: Anurag
authors.initials: A
authors.lastname: Sethi
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT, United States.
authors.forename: Declan
authors.initials: D
authors.lastname: Clarke
authors.affiliation: Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States.
authors.forename: Jieming
authors.initials: J
authors.lastname: Chen
authors.affiliation: Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, United States.
authors.forename: Sushant
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, United States.
authors.forename: Timur R
authors.initials: TR
authors.lastname: Galeev
authors.affiliation: Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States; Department of Chemistry, Yale University, New Haven, CT, United States.
authors.forename: Lynne
authors.initials: L
authors.lastname: Regan
authors.affiliation: Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, United States. Electronic address: mark@gersteinlab.org.
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
mesh_terms: D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007536:Isomerism; D009154:Mutation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D011506:Proteins