Protein structure determination using metagenome sequence data

Despite decades of work by structural biologists, there are still ~5200 protein families with unknown structure outside the range of comparative modeling. We show that Rosetta structure prediction guided by residue-residue contacts inferred from evolutionary information can accurately model proteins that belong to large families and that metagenome sequence data more than triple the number of protein families with sufficient sequences for accurate modeling. We then integrate metagenome data, contact-based structure matching, and Rosetta structure calculations to generate models for 614 protein families with currently unknown structures; 206 are membrane proteins and 137 have folds not represented in the…

• UD
  U.S. Department of Energy

  Awards: -AC02-05CH11231, 05CH11231, AC02-05CH11231, DE-AC02, DE-AC02-05CH11231, DE-AC02-
• JG
  Joint Genome Institute

  Awards: DE-AC02-05CH11231, AC02-05CH11231
• NI
  National Institutes of Health

  Awards: R01GM092802, DE-AC02-05CH11231
• OO
  Office of Science

  Awards: AC02-05CH11231, -AC02-05CH11231, DE-AC02
• NI
  National Institute of General Medical Sciences

  Award: DE-AC02-05CH11231