Röder Konstantin, Wales David J
Department of Chemistry , University of Cambridge , Lensfield Road , Cambridge CB2 1EW , U.K.
J Phys Chem Lett. 2018 Nov 1;9(21):6169-6173. doi: 10.1021/acs.jpclett.8b02839. Epub 2018 Oct 11.
The study of energy landscapes has led to a good understanding of how and why proteins and nucleic acids adopt their native structure. Through evolution, sequences have adapted until they exhibit a strongly funneled energy landscape, stabilizing the native fold. Design of artificial biomolecules faces the challenge of creating similar stable, minimally frustrated, and functional sequences. Here we present a biminimization approach, mutational basin-hopping, in which we simultaneously use global optimization to optimize the energy and a target function describing a desired property of the system. This optimization of structure and sequence is a generalized basin-hopping method and produces an efficient design process, which can target properties such as binding affinity or solubility.
对能量景观的研究有助于很好地理解蛋白质和核酸如何以及为何采用其天然结构。通过进化，序列不断适应，直到呈现出强烈漏斗状的能量景观，从而稳定天然折叠结构。人工生物分子的设计面临着创造出类似的稳定、最小受挫且具有功能的序列的挑战。在此，我们提出一种双最小化方法——突变盆地跳跃法，即我们同时使用全局优化来优化能量以及描述系统所需特性的目标函数。这种结构和序列的优化是一种广义的盆地跳跃法，可产生高效的设计过程，该过程能够针对诸如结合亲和力或溶解度等特性。
