探究堆积特异性在蛋白质设计中的作用。
Probing the role of packing specificity in protein design.
作者信息
Dahiyat B I, Mayo S L
机构信息
Division of Chemistry and Chemical Engineering, California Institute of Technology, Mail Code 147-75, Pasadena, CA 91125, USA.
出版信息
Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10172-7. doi: 10.1073/pnas.94.19.10172.
By using a protein-design algorithm that quantitatively considers side-chain packing, the effect of specific steric constraints on protein design was assessed in the core of the streptococcal protein G beta1 domain. The strength of packing constraints used in the design was varied, resulting in core sequences that reflected differing amounts of packing specificity. The structural flexibility and stability of several of the designed proteins were experimentally determined and showed a trend from well-ordered to highly mobile structures as the degree of packing specificity in the design decreased. This trend both demonstrates that the inclusion of specific packing interactions is necessary for the design of native-like proteins and defines a useful range of packing specificity for the design algorithm. In addition, an analysis of the modeled protein structures suggested that penalizing for exposed hydrophobic surface area can improve design performance.
通过使用一种定量考虑侧链堆积的蛋白质设计算法，在链球菌蛋白G β1结构域的核心区域评估了特定空间位阻约束对蛋白质设计的影响。设计中使用的堆积约束强度有所变化，从而产生了反映不同堆积特异性程度的核心序列。对几种设计蛋白质的结构灵活性和稳定性进行了实验测定，结果表明，随着设计中堆积特异性程度的降低，结构呈现出从有序到高度灵活的趋势。这一趋势既表明了包含特定堆积相互作用对于设计类似天然蛋白质的必要性，也为设计算法定义了一个有用的堆积特异性范围。此外，对模拟蛋白质结构的分析表明，对暴露的疏水表面积进行惩罚可以提高设计性能。
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