Boda Dezso, Valiskó Mónika, Henderson Douglas, Gillespie Dirk, Eisenberg Bob, Gilson Michael K
Department of Physical Chemistry, University of Pannonia, Veszprém, Hungary.
Biophys J. 2009 Feb 18;96(4):1293-306. doi: 10.1016/j.bpj.2008.10.059.
Proteins can be influenced strongly by the electrolyte in which they are dissolved, and we wish to model, understand, and ultimately control such ionic effects. Relatively detailed Monte Carlo (MC) ion simulations are needed to capture biologically important properties of ion channels, but a simpler treatment of ions, the linearized Poisson-Boltzmann (LPB) theory, is often used to model processes such as binding and folding, even in settings where the LPB theory is expected to be inaccurate. This study uses MC simulations to assess the reliability of the LPB theory for such a system, the constrained, anionic active site of HIV protease. We study the distributions of ions in and around the active site, as well as the energetics of displacing ions when a protease inhibitor is inserted into the active site. The LPB theory substantially underestimates the density of counterions in the active site when divalent cations are present. It also underestimates the energy cost of displacing these counterions, but the error is not consequential because the energy cost is less than kBT, according to the MC calculations. Thus, the LPB approach will often be suitable for studying energetics, but the more detailed MC approach is critical when ionic distributions and fluxes are at issue.
蛋白质会受到其溶解所在电解质的强烈影响，我们希望对这种离子效应进行建模、理解并最终加以控制。需要进行相对详细的蒙特卡罗（MC）离子模拟来捕捉离子通道的生物学重要特性，但对于离子的一种更简单处理方法——线性化泊松 - 玻尔兹曼（LPB）理论，即使在预计该理论不准确的情况下，也常常被用于对诸如结合和折叠等过程进行建模。本研究使用MC模拟来评估LPB理论对于这样一个系统——HIV蛋白酶的受限阴离子活性位点——的可靠性。我们研究了活性位点内部及周围离子的分布情况，以及当一种蛋白酶抑制剂插入活性位点时置换离子的能量学。当存在二价阳离子时，LPB理论大幅低估了活性位点中抗衡离子的密度。它还低估了置换这些抗衡离子的能量成本，但根据MC计算，由于能量成本小于kBT，所以该误差并不重要。因此，LPB方法通常适用于研究能量学，但当涉及离子分布和通量问题时，更详细的MC方法至关重要。
