Department of Biology, Santa Clara University, 500 El Camino Real, Santa Clara, CA 95053, USA.
Protein Eng Des Sel. 2022 Feb 17;35. doi: 10.1093/protein/gzac001.
Protein stability, dynamics and function are intricately linked. Accordingly, protein designers leverage dynamics in their designs and gain insight to their successes and failures by analyzing their proteins' dynamics. Molecular dynamics (MD) simulations are a powerful computational tool for quantifying both local and global protein dynamics. This review highlights studies where MD simulations were applied to characterize the stability and dynamics of designed proteins and where dynamics were incorporated into computational protein design. First, we discuss the structural basis underlying the extreme stability and thermostability frequently observed in computationally designed proteins. Next, we discuss examples of designed proteins, where dynamics were not explicitly accounted for in the design process, whose coordinated motions or active site dynamics, as observed by MD simulation, enhanced or detracted from their function. Many protein functions depend on sizeable or subtle conformational changes, so we finally discuss the computational design of proteins to perform a specific function that requires consideration of motion by multi-state design.
蛋白质的稳定性、动态性和功能是错综复杂地联系在一起的。因此，蛋白质设计人员在设计中利用动力学，并通过分析蛋白质的动力学来获得对其成功和失败的深入了解。分子动力学（MD）模拟是一种强大的计算工具，可用于量化局部和全局蛋白质动力学。这篇综述强调了将 MD 模拟应用于描述设计蛋白质的稳定性和动力学的研究，以及将动力学纳入计算蛋白质设计的研究。首先，我们讨论了在计算设计的蛋白质中经常观察到的极端稳定性和热稳定性的结构基础。接下来，我们讨论了一些设计蛋白质的例子，在这些例子中，动力学在设计过程中没有被明确考虑到，而通过 MD 模拟观察到的协调运动或活性位点动力学增强或削弱了它们的功能。许多蛋白质功能依赖于相当大或微妙的构象变化，因此我们最后讨论了蛋白质的计算设计，以执行特定的功能，这需要考虑通过多态设计进行的运动。
