Bò Leonardo, Milanetti Edoardo, Chen Cheng Giuseppe, Ruocco Giancarlo, Amadei Andrea, D'Abramo Marco
Department of Physics, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Center for Life Nano & Neuroscience, Italian Institute of Technology, Viale Regina Elena 291, 00161 Rome, Italy.
ACS Omega. 2022 Apr 12;7(16):13448-13454. doi: 10.1021/acsomega.1c06206. eCollection 2022 Apr 26.
We characterize the folding-unfolding thermodynamics of two mutants of the miniprotein Trp-cage by combining extended molecular dynamics simulations and an advanced statistical-mechanical-based approach. From a set of molecular dynamics simulations in an explicit solvent performed along a reference isobar, we evaluated the structural and thermodynamic behaviors of a mesophilic and a thermophilic mutant of the Trp-cage and their temperature dependence. In the case of the thermophilic mutant, computational data confirm that our theoretical-computational approach is able to reproduce the available experimental estimate with rather good accuracy. On the other hand, the mesophilic mutant does not show a clear two-state (folded and unfolded) behavior, preventing us from reconstructing its thermodynamics; thus, an analysis of its structural behavior along a reference isobar is presented. Our results show that an extended sampling of these kinds of systems coupled to an advanced statistical-mechanical-based treatment of the data can provide an accurate description of the folding-unfolding thermodynamics along a reference isobar, rationalizing the discrepancies between the simulated and experimental systems.
我们通过结合扩展分子动力学模拟和基于先进统计力学的方法，对小蛋白色氨酸笼（Trp-cage）的两个突变体的折叠-去折叠热力学进行了表征。通过沿着参考等压线在显式溶剂中进行的一组分子动力学模拟，我们评估了色氨酸笼的一个嗜温突变体和一个嗜热突变体的结构和热力学行为及其对温度的依赖性。对于嗜热突变体，计算数据证实我们的理论计算方法能够以相当高的精度重现现有的实验估计值。另一方面，嗜温突变体没有表现出明显的两态（折叠和未折叠）行为，这使得我们无法重构其热力学；因此，本文给出了其沿着参考等压线的结构行为分析。我们的结果表明，对这类系统进行扩展采样并结合基于先进统计力学的数据处理方法，可以准确描述沿着参考等压线的折叠-去折叠热力学，从而解释模拟系统和实验系统之间的差异。
