DOI: 10.1073/pnas.1931882100. Coarse-grained sequences for protein folding and design

Coarse-grained sequences for protein folding and design

10.1073/pnas.1931882100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We present the results of sequence design on our off-lattice minimalist model in which no specification of native-state tertiary contacts is needed. We start with a sequence that adopts a target topology and build on it through sequence mutation to produce new sequences that comprise distinct members within a target fold class. In this work, we use the α/β ubiquitin fold class and design two new sequences that, when characterized through folding simulations, reproduce the differences in folding mechanism seen experimentally for proteins L and G. The primary implication of this work is that patterning of hydrophobic and hydrophilic residues is the physical origin for the success of relative contact-order descriptions of folding, and that these physics-based potentials provide a predictive connection between free energy landscapes and amino acid sequence (the original protein folding problem). We present results of the sequence mapping from a 20- to the three-letter code for determining a sequence that folds into the WW domain topology to illustrate future extensions to protein design.

Bibliography

Brown, S., Fawzi, N. J., & Head-Gordon, T. (2003). Coarse-grained sequences for protein folding and design. Proceedings of the National Academy of Sciences, 100(19), 10712â10717.

Authors 3

Scott Brown (first)
Nicolas J. Fawzi (additional)
Teresa Head-Gordon (additional)

References 42 Referenced 102

Dates

Type	When
Created	21 years, 11 months ago (Sept. 16, 2003, 1:42 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 2:12 p.m.)
Indexed	1 month, 2 weeks ago (July 7, 2025, 7:44 a.m.)
Issued	21 years, 11 months ago (Sept. 8, 2003)
Published	21 years, 11 months ago (Sept. 8, 2003)
Published Online	21 years, 11 months ago (Sept. 8, 2003)
Published Print	21 years, 11 months ago (Sept. 16, 2003)

Funders 0

None

BibTeX

@article{Brown_2003, title={Coarse-grained sequences for protein folding and design}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1931882100}, DOI={10.1073/pnas.1931882100}, number={19}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Brown, Scott and Fawzi, Nicolas J. and Head-Gordon, Teresa}, year={2003}, month=sep, pages={10712–10717} }

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