Department of Biophysics, Faculty of Biological Science, Tarbiat Modares University, Tehran, 14115_111, Iran.
Sci Rep. 2023 Aug 30;13(1):14179. doi: 10.1038/s41598-023-40818-x.
Proteins are not static but are flexible molecules that can adopt many different conformations. The HIV-1 protease is an important target for the development of therapies to treat AIDS, due to its critical role in the viral life cycle. We investigated several dynamics studies on the HIV-1 protease families to illustrate the significance of examining the dynamic behaviors and molecular motions for an entire understanding of their dynamics-structure-function relationships. Using computer simulations and principal component analysis approaches, the dynamics data obtained revealed that: (i) The flap regions are the most obvious sign of the evolution of conformational dynamics in HIV-1 protease; (ii) There are dynamic structural regions in some proteins that contribute to the biological function and allostery of proteins via appropriate flexibility. These regions are a clear sign of the evolution of conformational dynamics of proteins, which we call dynamozones. The flap regions are one of the most important dynamozones members that are critical for HIV-1 protease function. Due to the existence of other members of dynamozones in different proteins, we propose to consider dynamozones as a footprint of the evolution of the conformational dynamics of proteins.
蛋白质不是静态的，而是具有柔韧性的分子，可以采用许多不同的构象。HIV-1 蛋白酶是开发治疗艾滋病疗法的重要靶点，因为它在病毒生命周期中起着关键作用。我们研究了 HIV-1 蛋白酶家族的几种动力学研究，以说明检查整个动力学-结构-功能关系中动态行为和分子运动的重要性。使用计算机模拟和主成分分析方法，获得的动力学数据表明：（i）瓣区是 HIV-1 蛋白酶构象动力学进化的最明显标志；（ii）在某些蛋白质中存在动态结构区域，这些区域通过适当的灵活性为蛋白质的生物功能和变构作用做出贡献。这些区域是蛋白质构象动力学进化的明显标志，我们称之为动力区。瓣区是最重要的动力区成员之一，对 HIV-1 蛋白酶功能至关重要。由于不同蛋白质中存在其他动力区成员，我们建议将动力区视为蛋白质构象动力学进化的足迹。
