PDF(Pubmed)
Abstract：
The intricate structural organization of the human nucleus is fundamental to cellular function and gene regulation. Recent advancements in experimental techniques, including high-throughput sequencing and microscopy, have provided valuable insights into nuclear organization. Computational modeling has played significant roles in interpreting experimental observations by reconstructing high-resolution structural ensembles and uncovering organization principles. However, the absence of standardized modeling tools poses challenges for furthering nuclear investigations. We present OpenNucleome-an open-source software designed for conducting GPU-accelerated molecular dynamics simulations of the human nucleus. OpenNucleome offers particle-based representations of chromosomes at a resolution of 100 KB, encompassing nuclear lamina, nucleoli, and speckles. This software furnishes highly accurate structural models of nuclear architecture, affording the means for dynamic simulations of condensate formation, fusion, and exploration of non-equilibrium effects. We applied OpenNucleome to uncover the mechanisms driving the emergence of \'fixed points\' within the nucleus-signifying genomic loci robustly anchored in proximity to specific nuclear bodies for functional purposes. This anchoring remains resilient even amidst significant fluctuations in chromosome radial positions and nuclear shapes within individual cells. Our findings lend support to a nuclear zoning model that elucidates genome functionality. We anticipate OpenNucleome to serve as a valuable tool for nuclear investigations, streamlining mechanistic explorations and enhancing the interpretation of experimental observations.
摘要：
人类细胞核复杂的结构组织是细胞功能和基因调控的基础。实验技术的最新进展，包括高通量测序和显微镜，为核组织提供了宝贵的见解。计算模型通过重建高分辨率结构集合和揭示组织原理，在解释实验观察方面发挥了重要作用。然而,缺乏标准化的建模工具对进一步进行核调查提出了挑战。我们介绍了OpenNucleome-一种开源软件，用于进行GPU加速的人核分子动力学模拟。OpenNucleome以100KB的分辨率提供基于粒子的染色体表示，包括核层，核仁,和斑点。该软件提供了高度精确的核体系结构结构模型，提供凝析油形成的动态模拟手段，聚变,以及非均衡效应的探索。我们应用OpenNucleome来揭示驱动“固定点”出现的机制，这些“固定点”在核标志基因组基因座中稳固地锚定在特定核体附近，以实现功能目的。即使在单个细胞内染色体径向位置和细胞核形状的显着波动中，这种锚定仍保持弹性。我们的发现为阐明基因组功能的核分区模型提供了支持。我们预计OpenNucleome将成为核调查的宝贵工具，简化机械探索，增强实验观察的解释。
