Heparin is a natural highly sulfated unbranched periodic polysaccharide that plays a critical role in regulating various cellular events through interactions with its protein targets such as growth factors and cytokines. Although all-atom simulations of heparin-containing systems provide valuable insights into their structural and dynamical properties, long chains of heparin participate in many biologically relevant processes at much bigger scales and longer times than the ones which all-atom MD is able to effectively deal with. Among these processes is the establishment of chemokine gradients, amyloidogenesis, or collagen network organization. To address this limitation, coarse-grained models simplify these systems by reducing the number of degrees of freedom, allowing for the efficient exploration of structural changes within protein/heparin complexes. We introduce and validate the accuracy of a new coarse-grained physics-based model designed for studying protein/heparin interactions, which has been incorporated into the UNRES software package. The effective energy functions from UNRES and SUGRES-1P have been employed for the protein and heparin components, respectively. A good agreement between the obtained coarse-grained simulation results and experimental data confirms the suitability of the combined coarse-grained UNRES and SUGRES-1P model for in silico analysis of complex biological phenomena involving heparin, spanning time scales and molecular system sizes not attainable by conventional atomistic molecular dynamics simulations.

中文翻译：

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实施肝素的 UNRES/SUGRES-1P 粗粒模型，用于模拟蛋白质/肝素相互作用。


肝素是一种天然的高度硫酸化、无支链的周期性多糖，通过与生长因子和细胞因子等蛋白质靶标的相互作用，在调节各种细胞事件中起关键作用。尽管含肝素系统的全原子模拟为了解其结构和动力学特性提供了有价值的见解，但肝素的长链参与许多生物学相关过程的规模和时间比全原子 MD 能够有效处理的过程要大得多。这些过程包括趋化因子梯度、淀粉样蛋白生成或胶原蛋白网络组织的建立。为了解决这一限制，粗粒度模型通过减少自由度数量来简化这些系统，从而可以有效地探索蛋白质/肝素复合物内的结构变化。我们引入并验证了一种新的基于粗粒度物理的模型的准确性，该模型旨在研究蛋白质/肝素相互作用，该模型已被纳入 UNRES 软件包。UNRES 和 SUGRES-1P 的有效能量函数已分别用于蛋白质和肝素成分。获得的粗粒度模拟结果与实验数据之间的良好一致性证实了粗粒度 UNRES 和 SUGRES-1P 组合模型适用于涉及肝素的复杂生物现象的计算机分析，跨越时间尺度和分子系统大小是传统原子分子动力学模拟无法达到的。