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Obtaining transition rates from single-channel data without initial parameter seeding.
Channels ( IF 3.3 ) Pub Date : 2020-02-29 , DOI: 10.1080/19336950.2020.1732004
Michael Voldsgaard Clausen 1
Affiliation  

Background and Purpose: Ion-channels are membrane proteins that can adopt several distinct structural conformations. Some of the conformations are open and allow the passage of ions through the membrane; others are closed and hinder ion flow. Patch-clamp recordings of single ion-channels show if a channel is open or closed, but does not immediately reveal the underlying mechanism, which typically includes several open and closed conformations.With kinetic analysis of single-channel data, sequences of observed open and closed times are fitted to proposed schemes to deduct the underlying kinetics of the ion-channel. Current programs to perform kinetic analysis uses initial parameter guessing. Here an alternative approach that uses a global fitting procedure and no initial parameter seeding is developed and tested.Methods: Different fitting algorithms that use variations and combinations of Simplex-optimization, Genetic Algorithm and Particle Swarm are tested against simulated data with brief events removed as in real resolution limited data.Results: A two-step fitting algorithm that uses Particle Swarm optimization to find initial parameters and then a modified Simplex approach to fine-adjust the initial parameters successfully find the correct rates used for data simulation.Conclusions: SCAIM (Single Channel Analysis in MATLAB) facilitate the deduction of kinetic schemes underlying single-channel data.

中文翻译:

在没有初始参数播种的情况下从单通道数据获取转换速率。

背景与目的:离子通道是一种膜蛋白,可以采用几种不同的结构构象。一些构象是开放的,并允许离子通过膜。其他则关闭并阻碍离子流动。单个离子通道的膜片钳记录显示通道是打开还是关闭,但不能立即揭示潜在的机理,通常包括几个打开和关闭的构型。通过对单通道数据进行动力学分析,观察到的打开和关闭序列封闭时间适合拟议的方案,以推导离子通道的基本动力学。当前执行动力学分析的程序使用初始参数猜测。在这里,开发并测试了使用全局拟合过程且没有初始参数播种的替代方法。
更新日期:2020-04-20
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