On the perturbation nature of allostery: sites, mutations, and signal modulation
On the perturbation nature of allostery: sites, mutations, and signal modulation
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DOI：
10.1016/j.sbi.2018.10.008
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发表时间：
2019-06-01
影响因子：
6.8
通讯作者：
Berezovsky, Igor N.
中科院分区：
文献类型：
--
作者：
Guarnera, Enrico;Berezovsky, Igor N.
不管系统的多样性如何，异形信号总是由扰动引起的。变构的这种反复出现的特性为研究变构机理发展不同的实验努力和理论模型奠定了基础。在这里讨论的计算方法中，特别强调了基于结构的变构统计力学模型(SBSMMA)，它允许人们研究变构通信的因果关系和能量学。我们认为，基于SBSMMA的反向变构信号可以用来预测潜在的变构位点，并诱导可调的变构反应。还可以探索突变的每残基变构效应，并使用SBSMMA预测扩大癌症突变图景的“潜在驱动因素”。文中还讨论了计算模型在网络资源中的最新和最重要的实现，并对未来的研究方向进行了简要展望。
Regardless of the diversity of systems, allosteic signalling is found to be always caused by perturbations. This recurring trait of allostery serves as a foundation for developing different experimental efforts and theoretical models for the studies of allosteric mechanisms. Among computational approaches considered here particular emphasis is given to the structure-based statistical mechanical model of allostery (SBSMMA), which allows one to study the causality and energetics of allosteric communication. We argue that the reverse allosteric signaling on the basis of SBSMMA can be used for predicting latent allosteric sites and inducing a tunable allosteric response. Per-residue allosteric effects of mutations can also be explored and 'latent drivers' expanding the cancer mutational landscape can be predicted using SBSMMA. Most recent and important implementations of computational models in web-resources along with a brief outlook on future research directions are also discussed.