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DOI | 10.1126/science.aap7577 |
Comprehensive computational design of ordered peptide macrocycles | |
Hosseinzadeh, Parisa1,2; Bhardwaj, Gaurav1,2; Mulligan, Vikram Khipple1,2; Shortridge, Matthew D.3; Craven, Timothy W.1,2; Pardo-Avila, Fatima4; Retti, Stephen A.1,2; Kim, David E.1,2; Silva, Daniel-Adriano1,2; Ibrahim, Yehia M.5; Webb, Ian K.5; Cort, John R.5; Adkins, Joshua N.5; Varani, Gabriele3; Baker, David1,2,6 | |
2017-12-15 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 358期号:6369页码:1461-1466 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with L-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L- and c-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000417918500048 |
WOS关键词 | MOLECULAR-STRUCTURE DETERMINATION ; DE-NOVO DESIGN ; CONSTRAINED PEPTIDES ; CYCLIC-PEPTIDES ; XPLOR-NIH ; FUTURE ; LIBRARIES ; PROTEINS ; DRUGS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/197552 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Washington, Dept Biochem, Seattle, WA 98195 USA; 2.Univ Washington, Inst Prot Design, Seattle, WA 98195 USA; 3.Univ Washington, Dept Chem, Seattle, WA 98195 USA; 4.Stanford Univ, Dept Struct Biol, Sch Med, Stanford, CA 94305 USA; 5.Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA 99352 USA; 6.Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA |
推荐引用方式 GB/T 7714 | Hosseinzadeh, Parisa,Bhardwaj, Gaurav,Mulligan, Vikram Khipple,et al. Comprehensive computational design of ordered peptide macrocycles[J]. SCIENCE,2017,358(6369):1461-1466. |
APA | Hosseinzadeh, Parisa.,Bhardwaj, Gaurav.,Mulligan, Vikram Khipple.,Shortridge, Matthew D..,Craven, Timothy W..,...&Baker, David.(2017).Comprehensive computational design of ordered peptide macrocycles.SCIENCE,358(6369),1461-1466. |
MLA | Hosseinzadeh, Parisa,et al."Comprehensive computational design of ordered peptide macrocycles".SCIENCE 358.6369(2017):1461-1466. |
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