Department of Pharmacy and Biotechnology, Alma Mater Studiorum-Università di Bologna, via Belmeloro 6, 40126 Bologna, Italy.
Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
J Chem Inf Model. 2020 Dec 28;60(12):6532-6543. doi: 10.1021/acs.jcim.0c01179. Epub 2020 Dec 9.
In recent years, the K2P family of potassium channels has been the subject of intense research activity. Owing to the complex function and regulation of this family of ion channels, it is common practice to complement experimental findings with the atomistic description provided by computational approaches such as molecular dynamics (MD) simulations, especially, in light of the unprecedented timescales accessible at present. However, despite recent substantial improvements, the accuracy of MD simulations is still undermined by the intrinsic limitations of force fields. Here, we systematically assessed the performance of the most popular force fields employed to study ion channels at timescales that are orders of magnitude greater than the ones accessible when these energy functions were first developed. Using 32 μs of trajectories, we investigated the dynamics of a member of the K2P ion channel family, the TRAAK channel, using two established force fields in simulations of biological systems: AMBER and CHARMM. We found that while results are comparable on the nanosecond timescales, significant inconsistencies arise at microsecond timescales.
近年来，K2P 家族钾通道一直是研究活动的焦点。由于该家族离子通道的复杂功能和调节，通常需要将实验结果与计算方法（如分子动力学 (MD) 模拟）提供的原子描述相结合，尤其是在目前可获得的前所未有的时间尺度下。然而，尽管最近取得了实质性的进展，但 MD 模拟的准确性仍然受到力场的固有限制的影响。在这里，我们系统地评估了在远大于这些能量函数最初开发时可及的时间尺度上研究离子通道时使用的最流行的力场的性能。使用 32 μs 的轨迹，我们使用两种已建立的生物系统模拟力场（Amber 和 Charmm）研究了 K2P 离子通道家族的一个成员，即 TRAAK 通道的动力学。我们发现，虽然在纳秒时间尺度上的结果是可比的，但在微秒时间尺度上会出现显著的不一致。
