AMBER-DYES: Characterization of Charge Fluctuations and Force Field Parameterization of Fluorescent Dyes for Molecular Dynamics Simulations
AMBER-DYES: Characterization of Charge Fluctuations and Force Field Parameterization of Fluorescent Dyes for Molecular Dynamics Simulations
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DOI：
10.1021/ct500869p
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发表时间：
2014-12-01
影响因子：
5.5
通讯作者：
Grubmueller, Helmut
中科院分区：
文献类型：
--
作者：
Graen, Timo;Hoefling, Martin;Grubmueller, Helmut
单分子荧光实验和理论的最新进展允许直接比较和改进实验和模拟的解释。为此，需要与现有的生物分子力场相容并且可以整合到现有的生物分子力场中的用于大量染料的力场。在这里，我们开发，表征和实施AMBER-DYES，一个模块化的荧光标记力场，用于一组来自Alexa，Atto和Cy家族的22种荧光染料及其连接体，这些染料通常用于单分子光谱实验。力场与AMBER蛋白力场和GROMACS分子动力学模拟程序兼容。离域p电子轨道的高电子极化率，如在许多荧光染料中发现的，对基于点电荷的力场如AMBER提出了特别的挑战。为了量化由于电子极化率引起的电荷波动，我们在显式溶剂中模拟了22种染料，并在B3 LYP/6- 31 G *//TIP 3 P理论水平上使用QM/MM模拟对电荷波动进行了采样。模拟的分析使我们能够从多个轨迹的溶剂化电荷分布获得系综拟合RESP电荷。我们观察到广泛的，单峰电荷分布的共轭环原子具有明确定义的平均值。电荷拟合程序进行了验证，对公布的染料样氨基酸色氨酸，这表明与现有的色氨酸参数从琥珀色，CHARMM，和OPLS力场家庭的收费。的电荷波动的主成分分析表明，少数集体坐标足以描述大部分的面内染料极化率。AMBER-DYES力场允许快速制备荧光系统的所有原子分子动力学模拟，用于最先进的多微秒轨迹。
Recent advances in single molecule fluorescence experiments and theory allow a direct comparison and improved interpretation of experiment and simulation. To this end, force fields for a larger number of dyes are required which are compatible with and can be integrated into existing biomolecular force fields. Here, we developed, characterized, and implemented AMBER-DYES, a modular fluorescent label force field, for a set of 22 fluorescent dyes and their linkers from the Alexa, Atto, and Cy families, which are in common use for single molecule spectroscopy experiments. The force field is compatible with the AMBER protein force fields and the GROMACS molecular dynamics simulation program. The high electronic polarizability of the delocalized p-electron orbitals, as found in many fluorescent dyes, poses a particular challenge to point charge based force fields such as AMBER. To quantify the charge fluctuations due to the electronic polarizability, we simulated the 22 dyes in explicit solvent and sampled the charge fluctuations using QM/MM simulations at the B3LYP/6-31G*//TIP3P level of theory. The analysis of the simulations enabled us to derive ensemble fitted RESP charges from the solvated charge distributions of multiple trajectories. We observed broad, single peaked charge distributions for the conjugated ring atoms with well-defined mean values. The charge fitting procedure was validated against published charges of the dyelike amino acid tryptophan, which showed good agreement with existing tryptophan parameters from the AMBER, CHARMM, and OPLS force field families. A principal component analysis of the charge fluctuations revealed that a small number of collective coordinates suffices to describe most of the in-plane dye polarizability. The AMBER-DYES force field allows the rapid preparation of all atom molecular dynamics simulations of fluorescent systems for state of the art multi microsecond trajectories.