Department of Electrical and Computer Engineering, University of British Columbia, Vancouver V6T 1Z4, Canada.
IEEE/ACM Trans Comput Biol Bioinform. 2011 Jan-Mar;8(1):273-81. doi: 10.1109/TCBB.2008.136.
Constructing accurate computational models that explain how ions permeate through a biological ion channel is an important problem in biophysics and drug design. Brownian dynamics simulations are large-scale interacting particle computer simulations for modeling ion channel permeation but can be computationally prohibitive. In this paper, we show the somewhat surprising result that a small-dimensional semi-Markov model can generate events (such as conduction events and dwell times at binding sites in the protein) that are statistically indistinguishable from brownian dynamics computer simulation. This approach enables the use of extrapolation techniques to predict channel conduction when performing the actual brownian dynamics simulation that is computationally intractable. Numerical studies on the simulation of gramicidin A ion channels are presented.
构建能够解释离子如何穿过生物离子通道的精确计算模型是生物物理学和药物设计中的一个重要问题。布朗动力学模拟是用于模拟离子通道渗透的大规模相互作用粒子计算机模拟，但计算成本可能过高。在本文中，我们展示了一个有点令人惊讶的结果，即一个小维度的半马尔可夫模型可以产生与布朗动力学计算机模拟在统计学上无法区分的事件（例如传导事件和结合部位的停留时间）。这种方法使我们能够在进行实际布朗动力学模拟（该模拟在计算上难以处理）时，使用外推技术来预测通道传导。本文还展示了针对革兰氏菌素 A 离子通道模拟的数值研究。
