Publication Date:
2014-10-25
Description:
The design of protein sequences that fold into prescribed de novo structures is challenging. General solutions to this problem require geometric descriptions of protein folds and methods to fit sequences to these. The alpha-helical coiled coils present a promising class of protein for this and offer considerable scope for exploring hitherto unseen structures. For alpha-helical barrels, which have more than four helices and accessible central channels, many of the possible structures remain unobserved. Here, we combine geometrical considerations, knowledge-based scoring, and atomistic modeling to facilitate the design of new channel-containing alpha-helical barrels. X-ray crystal structures of the resulting designs match predicted in silico models. Furthermore, the observed channels are chemically defined and have diameters related to oligomer state, which present routes to design protein function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomson, Andrew R -- Wood, Christopher W -- Burton, Antony J -- Bartlett, Gail J -- Sessions, Richard B -- Brady, R Leo -- Woolfson, Derek N -- BB/J008990/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Oct 24;346(6208):485-8. doi: 10.1126/science.1257452.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. chzart@bristol.ac.uk d.n.woolfson@bristol.ac.uk. ; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK. ; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. ; School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK. ; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK. chzart@bristol.ac.uk d.n.woolfson@bristol.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342807" target="_blank"〉PubMed〈/a〉
Keywords:
*Computational Biology
;
*Models, Molecular
;
Peptides/chemistry
;
*Protein Structure, Secondary
;
Solubility
;
Water/*chemistry
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
