High-Performance Analysis of Biomolecular Containers to Measure Small-Molecule Transport, Transbilayer Lipid Diffusion, and Protein Cavities
High-Performance Analysis of Biomolecular Containers to Measure Small-Molecule Transport, Transbilayer Lipid Diffusion, and Protein Cavities
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DOI：
10.1021/acs.jcim.9b00324
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发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Perilla, Juan R.
中科院分区：
文献类型：
--
作者：
Bryer, Alexander J.;Hadden-Perilla, Jodi A.;Perilla, Juan R.
区室化是生物学的一个中心主题。细胞由许多膜封闭的结构组成，进化以促进特定的生化过程;病毒作为遗传物质的容器，优化以驱动感染。分子动力学模拟提供了一种机制来研究生物分子容器及其对环境的影响;然而，轨迹分析软件通常缺乏容器内部与外部的知识。此外，许多相关的容器分析涉及大规模的颗粒跟踪工作，这可能随着系统尺寸的增加而变得在计算上难以承受。在这里，提出了一种基于3-D射线投射的新方法，其快速分类任意形状的生物分子容器周围的空间，使得能够快速确定颗粒的身份和计数（例如，溶剂分子）。该方法广泛适用于容器的研究，并能够高性能表征的性质，如溶剂密度，小分子运输，跨双层脂质扩散，和蛋白质腔的拓扑结构。该方法在VMD中实现，VMD是一种广泛使用的模拟分析工具，支持个人计算机，云和并行超级计算机，包括ORNL的Summit和Titan以及NCSA的Blue沃茨，其中该方法可以用于有效地分析包含数百万个粒子的轨迹。在许多轨迹帧上快速表征颗粒相对于生物分子容器的空间关系的能力，而不管大颗粒计数，使得能够在以前不可行的尺度上以以前无法达到的准确度水平分析容器。
Compartmentalization is a central theme in biology. Cells are composed of numerous membrane-enclosed structures, evolved to facilitate specific biochemical processes; viruses act as containers of genetic material, optimized to drive infection. Molecular dynamics simulations provide a mechanism to study biomolecular containers and the influence they exert on their environments; however, trajectory analysis software generally lacks knowledge of container interior versus exterior. Further, many relevant container analyses involve large-scale particle tracking endeavors, which may become computationally prohibitive with increasing system size. Here, a novel method based on 3-D ray casting is presented, which rapidly classifies the space surrounding biomolecular containers of arbitrary shape, enabling fast determination of the identities and counts of particles (e.g., solvent molecules) found inside and outside. The method is broadly applicable to the study of containers and enables high-performance characterization of properties such as solvent density, small-molecule transport, transbilayer lipid diffusion, and topology of protein cavities. The method is implemented in VMD, a widely used simulation analysis tool that supports personal computers, clouds, and parallel supercomputers, including ORNL's Summit and Titan and NCSA's Blue Waters, where the method can be employed to efficiently analyze trajectories encompassing millions of particles. The ability to rapidly characterize the spatial relationships of particles relative to a biomolecular container over many trajectory frames, irrespective of large particle counts, enables analysis of containers on a scale that was previously unfeasible, at a level of accuracy that was previously unattainable.