Joseph Jerelle A, Röder Konstantin, Chakraborty Debayan, Mantell Rosemary G, Wales David J
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Chem Commun (Camb). 2017 Jun 27;53(52):6974-6988. doi: 10.1039/c7cc02413d.
The potential energy landscape perspective provides both a conceptual and a computational framework for predicting, understanding and designing molecular properties. In this Feature Article, we highlight some recent advances that greatly facilitate structure prediction and analysis of global thermodynamics and kinetics in proteins and nucleic acids. The geometry optimisation procedures, on which these calculations are based, can be accelerated significantly using local rigidification of selected degrees of freedom, and through implementations on graphics processing units. Results of progressive local rigidification are first summarised for trpzip1, including a systematic analysis of the heat capacity and rearrangement rates. Benchmarks for all the essential optimisation procedures are then provided for a variety of proteins. Applications are then illustrated from a study of how mutation affects the energy landscape for a coiled-coil protein, and for transitions in helix morphology for a DNA duplex. Both systems exhibit an intrinsically multifunnel landscape, with the potential to act as biomolecular switches.
势能景观视角为预测、理解和设计分子特性提供了一个概念性和计算性的框架。在这篇专题文章中，我们重点介绍了一些近期的进展，这些进展极大地促进了蛋白质和核酸的结构预测以及全局热力学和动力学分析。基于这些计算的几何优化程序，可以通过对选定自由度进行局部刚性化以及在图形处理单元上实现，从而显著加速。首先总结了色氨酸拉链1（trpzip1）渐进局部刚性化的结果，包括对热容和重排速率的系统分析。然后为各种蛋白质提供了所有基本优化程序的基准。接着通过研究突变如何影响卷曲螺旋蛋白的能量景观以及DNA双链体螺旋形态的转变来说明应用。这两个系统都呈现出本质上的多漏斗景观，具有作为生物分子开关的潜力。
