利用过渡界面采样的药物渗透精确动力学。

IF 2.9 2区 化学 Q3 CHEMISTRY, PHYSICAL
Sina Safaei*, , , Lukas Baldauf, , , Titus S. van Erp, , and , An Ghysels*, 
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引用次数: 0

摘要

我们实现了复制交换转换接口采样(RETIS)算法的最高级变体∞RETIS,它在无限交换限制中采用异步交换移动。这种设计可以实现跨cpu和gpu的高效并行化,从而大大加快收敛速度。利用分子动力学(MD)模拟,我们应用该方法研究了5-氨基乙酰丙酸(5-ALA)的膜渗透,5-氨基乙酰丙酸是一种广泛应用于光动力治疗(PDT)和荧光引导手术的亲水药物。关键的动力学性质,包括渗透率和平均首次通过时间,是根据得到的无偏轨迹计算出来的。此外,研究人员还探索了5-ALA渗透的机理细节,揭示了5-ALA的取向及其与膜内水分子的水合作用对轨迹是否有助于成功穿越膜的影响。通过解决5-ALA通过磷脂双分子层渗透的完整动力学机制,本研究展示了∞RETIS在解决生物学和药学相关系统中罕见事件动力学方面的力量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Exact Kinetics of Drug Permeation Using Transition Interface Sampling

Exact Kinetics of Drug Permeation Using Transition Interface Sampling

We implement ∞RETIS, the most advanced variant of the replica exchange transition interface sampling (RETIS) algorithm, which employs asynchronous swapping moves in the infinite swapping limit. This design enables highly efficient parallelization across CPUs and GPUs, resulting in a substantial acceleration in convergence. Using molecular dynamics (MD) simulations, we apply this method to investigate the membrane permeation of 5-aminolevulinic acid (5-ALA), a hydrophilic drug widely used in photodynamic therapy (PDT) and fluorescence-guided surgery. Key kinetic properties, including the permeability and mean first passage time, are computed from the resulting unbiased trajectories. Furthermore, the mechanistic details of 5-ALA permeation are explored, showing the impact of the 5-ALA orientation and its hydration by water molecules inside the membrane on whether a trajectory contributes to successful membrane crossing. By resolving the full kinetic mechanism of 5-ALA permeation through a phospholipid bilayer, this study showcases the power of ∞RETIS in addressing rare event dynamics in biologically and pharmaceutically relevant systems.

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来源期刊
CiteScore
5.80
自引率
9.10%
发文量
965
审稿时长
1.6 months
期刊介绍: An essential criterion for acceptance of research articles in the journal is that they provide new physical insight. Please refer to the New Physical Insights virtual issue on what constitutes new physical insight. Manuscripts that are essentially reporting data or applications of data are, in general, not suitable for publication in JPC B.
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