Computer Modeling and Theoretical Studies of Biopolymers

摘要：对DPPC双层中的水线进行了一系列经典的分子动力学模拟，得到了高达90ps的寿命tau=37？8ps(不包括在4ps内断裂的水线)。这足够长，可以通过量子力学的跳跃机制在双层中传导质子，类似于冰中的质子传导。在水/辛烷/水三明治状排列的辛烷区，导线的寿命本质上是相似的(&lt；tau&gt；=36？3ps)，表明水/辛烷体系在探索性膜研究中是有用的。这项研究的一份报告已经提交给了《化学物理杂志》。在分子动力学模拟中，非对称边界条件P21得到了与P1值相同的结果；Pc和P1值对前两个体系也是相同的。P21进一步在模拟中进行测试，包括在水中铺展辛烷膜，以及在两个小叶中包含不同数量的脂类的初始条件下DPPC双层的平衡。最后，在P21中对DOPC/蜂毒素膜的模拟表明，在表面上合理的初始条件下，脂类发生了显著的再分布。这些结果突出了模拟膜和其他具有非对称边界条件的非均相界面系统的有效性。这项研究的一份报告已经提交给了生物物理杂志。对DPPC双层分子进行了20 ns的分子动力学模拟，并与简单的脂质动力学模型进行了比较。一幅始终如一的图景出现了。单个脂类通过快速的内部运动，在100ps的时间尺度上将自己平均成相对圆柱形的形状，并在ns时间尺度上以锥形势能摆动。这些运动发生在高度流动的环境中，很像液态烷烃。由于双层/水界面的限制，脂类的横向扩散的时间尺度要长得多，而不是因为双层的内部粘性很高。这项研究的一份报告已经提交给了《化学研究》杂志。DOPC双层膜中水通道蛋白的模拟已经开始。初步结果表明，水的传输与实验观察一致，并可能解释为什么水通道蛋白可以传导质子，而不是水。

Summary: A series of classical molecular dynamics simulations of a water wire in a DPPC bilayer yielded lifetimes tau of up to 90 ps, with <tau> = 37 ? 8 ps (not including wires that broke within 4 ps). This is sufficiently long to conduct protons across the bilayer through a quantum mechanical hopping mechanism, similar to proton conduction in ice. Lifetimes of wires in the octane region of a water/octane/water sandwich-like arrangement were qualitatively similar (<tau> = 36 ?3 ps), demonstrating the usefulness of the water/octane system in exploratory membrane studies. A report of this research has been submitted for publication to the Journal of Chemical Physics. The asymmetric boundary condition P21 was shown to yield equivalent results to P1 in molecular dynamics simulations of bulk water, a water/vacuum interface, and pure DPPC bilayers with an equal numbers of lipids per leaflet; equivalence of Pc and P1 was also demonstrated for the former two systems. P21 was further tested in simulations involving the spreading of an octane film on water, and equilibration of a DPPC bilayer from an initial condition containing different number of lipids in the two leaflets. Lastly, a simulation of a DOPC/melittin membrane in P21 showed significant redistribution of lipids from an ostensibly reasonable initial condition. These results highlight the utility of simulating membranes and other heterogeneous interfacial systems with asymmetric boundary conditions. A report of this research has been submitted for publication to the Biophysical Journal. Results from a 20 ns molecular dynamcis simulation of a DPPC bilayer were compared with simple models of lipid dynamics. A consistent picture emerges. Individual lipids, through fast internal motions, average themselves into relatively cylindrical shapes on the 100 ps time scale, and wobble in a cone-like potential on the ns time scale. These motions take place in a highly fluid environment, much like a liquid alkane. Lateral diffusion of the lipids is on a significantly longer time scale because of restrictions at the bilayer/water interface, not because the interior of the bilayer is highly viscous. A report of this research has been submitted for publication to Accounts of Chemical Research. Simulations of aquaporin in a DOPC bilayer have commenced. Preliminary results show transport of water consistent with experimental observations, and potentially explain why aquaporin can conduct protons, but not water.