Department of Chemistry, Georgetown University, Washington, DC 20057, USA.
Department of Civil and Environmental Engineering, The George Washington University, Washington, DC 20052, USA.
J Chem Phys. 2017 Sep 28;147(12):125103. doi: 10.1063/1.5003823.
Positional fluctuations of an atom in a protein can be described as motion in an effective local energy minimum created by the surrounding protein atoms. The dependence of atomic fluctuations on both temperature (T) and pressure (P) has been used to probe the nature of these minima, which are generally described as harmonic in experiments such as x-ray crystallography and neutron scattering. Here, a quasiharmonic analysis method is presented in which the P-T dependence of atomic fluctuations is in terms of an intrinsic isobaric thermal expansivity α and an intrinsic isothermal compressibility κ. The method is tested on previously reported mean-square displacements from P-T molecular dynamics simulations of lysozyme, which were interpreted to have a pressure-independent dynamical transition T near 200 K and a change in the pressure dependence near 480 MPa. Our quasiharmonic analysis of the same data shows that the P-T dependence can be described in terms of α and κ where below T, the temperature dependence is frozen at the T value. In addition, the purported transition at 480 MPa is reinterpreted as a consequence of the pressure dependence of T and the quasiharmonic frequencies. The former also indicates that barrier heights between substates are pressure dependent in these data. Furthermore, the insights gained from this quasiharmonic analysis, which was of the energy landscape near the native state of a protein, suggest that similar analyses of other simulations may be useful in understanding such phenomena as pressure-induced protein unfolding.
蛋白质中原子的位置波动可以描述为在周围蛋白质原子形成的有效局部能量最低点的运动。原子波动对温度（T）和压力（P）的依赖性已被用于探测这些最低点的性质，这些最低点在 X 射线晶体学和中子散射等实验中通常被描述为谐波。在这里，提出了一种准谐分析方法，其中原子波动的 P-T 依赖性是用固有等压热膨胀率α和固有等体压缩率κ来表示的。该方法在先前报道的溶菌酶的 P-T 分子动力学模拟的均方位移上进行了测试，这些模拟结果被解释为在 200 K 左右存在与压力无关的动力学转变 T，以及在 480 MPa 左右压力依赖性的变化。我们对相同数据的准谐分析表明，可以用α和κ来描述 P-T 依赖性，其中在 T 以下，温度依赖性被冻结在 T 值。此外，在 480 MPa 处的所谓转变被重新解释为 T 的压力依赖性和准谐频率的结果。前者还表明，在这些数据中，亚稳态之间的势垒高度是压力依赖的。此外，从这种准谐分析中获得的关于蛋白质天然状态附近能量景观的见解表明，对其他模拟的类似分析可能有助于理解压力诱导蛋白质解折叠等现象。
