title: Protein structure determination using metagenome sequence data.
abstract: 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 Protein Data Bank. This approach provides the representative models for large protein families originally envisioned as the goal of the Protein Structure Initiative at a fraction of the cost.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98105, USA.|Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.|Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Ovchinnikov
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98105, USA.|Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.
authors.forename: Hahnbeom
authors.initials: H
authors.lastname: Park
authors.affiliation: Joint Genome Institute, Walnut Creek, CA 94598, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Varghese
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98105, USA.|Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.
authors.forename: Po-Ssu
authors.initials: PS
authors.lastname: Huang
authors.affiliation: Joint Genome Institute, Walnut Creek, CA 94598, USA.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Pavlopoulos
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98105, USA.|Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, WA 98105, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Kim
authors.affiliation: Facebook Inc., Seattle, WA 98109, USA.
authors.forename: Hetunandan
authors.initials: H
authors.lastname: Kamisetty
authors.affiliation: Joint Genome Institute, Walnut Creek, CA 94598, USA.|Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Nikos C
authors.initials: NC
authors.lastname: Kyrpides
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98105, USA. dabaker@u.washington.edu.|Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.|Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, WA 98105, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baker
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods*; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D019143:Evolution, Molecular; D054892:Metagenome; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D020539:Sequence Analysis, Protein; D012984:Software
chemical_list: D011506:Proteins