Protein stability by number: high-throughput and statistical approaches to one of protein science's most difficult problems.
Protein stability by number: high-throughput and statistical approaches to one of protein science's most difficult problems.
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DOI：
10.1016/j.cbpa.2011.03.015
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发表时间：
2011-06
影响因子：
7.8
通讯作者：
Sullivan, Brandon J.
中科院分区：
文献类型：
--
作者：
Magliery, Thomas J.;Lavinder, Jason J.;Sullivan, Brandon J.
大多数蛋白质只是勉强稳定，这阻碍了研究，使治疗应用复杂化，使蛋白质容易发生病理性不稳定突变。我们预测单点突变的热力学结果的能力仍然令人惊讶地有限，并且建立的测量稳定性的方法很慢。最近的进展使蛋白质稳定性研究进入高通量领域。一些方法是基于推断性读出，如活性、蛋白水解抗性或分裂蛋白片段重组。其他方法使用直接测量的小型化，例如固有荧光、H/D交换、半胱氨酸反应性、聚集和疏水染料结合（DSF）。基于统计分析（氨基酸的一致性和相关性）的蛋白质工程是有前途的，但仍有许多工作要理解和实施这些方法。
Most proteins are only barely stable, which impedes research, complicates therapeutic applications, makes proteins susceptible to pathologically destabilizing mutations. Our ability to predict the thermodynamic consequences of even single point mutations is still surprisingly limited, and established methods of measuring stability are slow. Recent advances are bringing protein stability studies into the high-throughput realm. Some methods are based on inferential read-outs such as activity, proteolytic resistance or split-protein fragment reassembly. Other methods use miniaturization of direct measurements, such as intrinsic fluorescence, H/D exchange, cysteine reactivity, aggregation and hydrophobic dye binding (DSF). Protein engineering based on statistical analysis (consensus and correlated occurrences of amino acids) is promising, but much work remains to understand and implement these methods.
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DOI：
10.1038/nsb1001-879
发表时间：
2001-10-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Ghaemmaghami, S;Oas, TG
通讯作者：
Oas, TG
影响因子：
46.9
作者：
Cabantous, S;Terwilliger, TC;Waldo, GS
通讯作者：
Waldo, GS
DOI：
10.1073/pnas.0910421107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Isom, Daniel G.;Vardy, Eyal;Hellinga, Homme W.
通讯作者：
Hellinga, Homme W.
影响因子：
46.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0304533101
发表时间：
2004-01-13
影响因子：
11.1
作者：
Ignatova, Z;Gierasch, LM
通讯作者：
Gierasch, LM