title: Ab initio prediction of the three-dimensional structure of a de novo designed protein: a double-blind case study.
abstract: Ab initio structure prediction and de novo protein design are two problems at the forefront of research in the fields of structural biology and chemistry. The goal of ab initio structure prediction of proteins is to correctly characterize the 3D structure of a protein using only the amino acid sequence as input. De novo protein design involves the production of novel protein sequences that adopt a desired fold. In this work, the results of a double-blind study are presented in which a new ab initio method was successfully used to predict the 3D structure of a protein designed through an experimental approach using binary patterned combinatorial libraries of de novo sequences. The predicted structure, which was produced before the experimental structure was known and without consideration of the design goals, and the final NMR analysis both characterize this protein as a 4-helix bundle. The similarity of these structures is evidenced by both small RMSD values between the coordinates of the two structures and a detailed analysis of the helical packing.
authors.affiliation: Department of Chemical Engineering, Princeton University, Princeton, New Jersey 08544-5263, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Klepeis
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wei
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hecht
authors.forename: Christodoulos A
authors.initials: CA
authors.lastname: Floudas
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry*; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D030562:Databases, Protein; D004311:Double-Blind Method; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D019151:Peptide Library; D011487:Protein Conformation; D011489:Protein Denaturation; D015202:Protein Engineering / Q000379:methods*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D020539:Sequence Analysis, Protein; D012984:Software
chemical_list: D000596:Amino Acids; D019151:Peptide Library; D011506:Proteins