High-Resolution Protein Design with Backbone Freedom
- 20 November 1998
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 282 (5393), 1462-1467
- https://doi.org/10.1126/science.282.5393.1462
Abstract
Recent advances in computational techniques have allowed the design of precise side-chain packing in proteins with predetermined, naturally occurring backbone structures. Because these methods do not model protein main-chain flexibility, they lack the breadth to explore novel backbone conformations. Here the de novo design of a family of α-helical bundle proteins with a right-handed superhelical twist is described. In the design, the overall protein fold was specified by hydrophobic-polar residue patterning, whereas the bundle oligomerization state, detailed main-chain conformation, and interior side-chain rotamers were engineered by computational enumerations of packing in alternate backbone structures. Main-chain flexibility was incorporated through an algebraic parameterization of the backbone. The designed peptides form α-helical dimers, trimers, and tetramers in accord with the design goals. The crystal structure of the tetramer matches the designed structure in atomic detail.Keywords
This publication has 49 references indexed in Scilit:
- De Novo protein design: towards fully automated sequence selection 1 1Edited by P. E. WrightJournal of Molecular Biology, 1997
- Hyperthermostable Surface Layer Protein Tetrabrachion from the ArchaebacteriumStaphylothermus marinus: Evidence for the Presence of a Right-handed Coiled Coil Derived from the Primary StructureJournal of Molecular Biology, 1996
- Application of a Self-consistent Mean Field Theory to Predict Protein Side-chains Conformation and Estimate Their Conformational EntropyJournal of Molecular Biology, 1994
- Principles determining the structure of β-sheet barrels in proteins I. A theoretical analysisJournal of Molecular Biology, 1994
- Contribution of Hydration to Protein Folding Thermodynamics: II. The Entropy and Gibbs Energy of HydrationJournal of Molecular Biology, 1993
- Free R value: a novel statistical quantity for assessing the accuracy of crystal structuresNature, 1992
- Prediction of protein side-chain conformation by packing optimizationJournal of Molecular Biology, 1991
- Tertiary templates for proteinsJournal of Molecular Biology, 1987
- CHARMM: A program for macromolecular energy, minimization, and dynamics calculationsJournal of Computational Chemistry, 1983
- The interpretation of protein structures: Estimation of static accessibilityJournal of Molecular Biology, 1971