ACCURATE PREDICTION OF THE STABILITY AND ACTIVITY EFFECTS OF SITE-DIRECTED MUTAGENESIS ON A PROTEIN CORE
ACCURATE PREDICTION OF THE STABILITY AND ACTIVITY EFFECTS OF SITE-DIRECTED MUTAGENESIS ON A PROTEIN CORE
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DOI：
10.1038/352448a0
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发表时间：
1991-08-01
期刊：
影响因子：
64.8
通讯作者：
LEVITT, M
中科院分区：
文献类型：
--
作者：
LEE, C;LEVITT, M
蛋白质结构、稳定性和活性的理论预测是分子生物学中尚未解决的重要问题，它将用于指导定点诱变和其他蛋白质工程技术。x射线衍射研究为许多蛋白质提供了广泛的结构信息，这对理论家提出了挑战，要求他们开发出可靠的技术，能够利用这些知识作为预测突变体特征的基础。本文报道了Lim和Sauer实验表征的78个lambda-repressor三位点序列变体的稳定化能的理论计算。计算出的能量与突变体的实测活动相对应；鉴别活性和非活性突变的可靠性为92%。它们甚至与突变体的热稳定性更直接相关，正确地识别出其中两种突变体比野生型更稳定。
THEORETICAL prediction of the structure, stability and activity of proteins, an important unsolved problem in molecular biology, would be of use for guiding site-directed mutagenesis and other protein-engineering techniques. X-ray diffraction studies have provided extensive structural information for many proteins, challenging theorists to develop reliable techniques able to use such knowledge as a base for prediction of mutants' characteristics. Here we report theoretical calculation of stabilization energies for 78 triple-site sequence variants of lambda-repressor characterized experimentally by Lim and Sauer 1. The calculated energies correlate with the mutants' measured activities; active and inactive mutations are discriminated with 92% reliability. They correlate even more directly with the mutants' thermostabilities, correctly identifying two of the mutants to be more stable than the wild type.