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Biology

Protein AKIL: A Tezgahı Published: July 25, 2013 doi: 10.3791/50476
Automatic Translation
1, 1, 1, 1, 1
1Department of Chemical and Biological Engineering, Princeton University

Abstract

De novo protein tasarım amacı, doğal diziye göre bu tür bir bağlanma afinitesi, agonist ya da antagonist davranış veya stabilite gibi belirli özellikleri, iyileştirmeler ile arzu edilen bir 3-boyutlu yapı içine düşen doyurmaya amino asit dizileri bulmaktır. Protein tasarım güncel gelişmeler ilaç tasarımı ve keşif merkezinde yer almaktadır. Sadece protein tasarım potansiyel olarak yararlı ilaç hedefleri için tahminler sağlar, ama aynı zamanda protein katlanması süreci ve protein-protein etkileşimleri anlayışımızı artırır yok. Bu yönlendirilmiş evrim gibi deneysel yöntemlerle protein tasarımı başarı göstermiştir. Ancak, bu tür yöntemleri tractably aranabilir sınırlı dizisi boşluk sınırlıdır. Bunun aksine, hesaplama tasarım stratejileri özellikler ve işlevler geniş bir yelpazede kapsayan dizileri çok daha büyük bir dizi tarama için izin verir. Biz hesaplama de novo protein tasarım metodoloji bir dizi geliştirdikprotein tasarım birçok önemli alanlarda mücadele yeteneğine ds. Bu artan bağlanma afinitesi açısından daha yüksek kararlılık ve kompleksleri için monomerik protein tasarımı içerir.

Daha geniş için bu yöntemleri yaymak için biz Protein AKIL (mevcut kullanmak http://www.proteinwisdom.org ), protein tasarım sorunları çeşitli için otomatik yöntemler sağlayan bir araçtır. Yapısal şablonları tasarım süreci başlatmak için sunulur. Tasarım ilk aşaması sırası alanda potansiyel enerji minimizasyonu yoluyla istikrarı geliştirmek amaçlayan bir optimizasyon sırası seçim aşamasıdır. Seçilen dizileri daha sonra bir kat özgüllük sahne ve bir bağlanma afinitesi sahne aracılığıyla çalıştırılır. Sürecinin her adımı için dizilerin bir rütbe-sipariş listesi birlikte ilgili tasarlanmış yapıları, tasarım kapsamlı bir nicel değerlendirme ile kullanıcıya sunar. Burada ayrıntıları o sağlamakm, her bir tasarım yöntemi, hem de yöntemlerin kullanımı ile elde birkaç önemli deneysel başarılar.

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Protein AKIL: A Tezgahı<em&gt; Siliko olarak</em&gt;<em&gt; De novo</emBiyomoleküllerin&gt; Tasarım
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Smadbeck, J., Peterson, M. B.,… More

Smadbeck, J., Peterson, M. B., Khoury, G. A., Taylor, M. S., Floudas, C. A. Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules. J. Vis. Exp. (77), e50476, doi:10.3791/50476 (2013).

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