Biomolecular Simulations Group, Institut Pasteur de Montevideo , Mataojo 2020, Montevideo CP 11400, Uruguay.
J Chem Theory Comput. 2017 Oct 10;13(10):5106-5116. doi: 10.1021/acs.jctc.7b00659. Epub 2017 Sep 20.
Viruses are tremendously efficient molecular devices that optimize the packing of genetic material using a minimalistic number of proteins to form a capsid or envelope that protects them from external threats, being also part of cell recognition, fusion, and budding machineries. Progress in experimental techniques has provided a large number of high-resolution structures of viruses and viruslike particles (VLP), while molecular dynamics simulations may furnish lively and complementary insights on the fundamental forces ruling viral assembly, stability, and dynamics. However, the large size and complexity of these macromolecular assemblies pose significant computational challenges. Alternatively, Coarse-Grained (CG) methods, which resign atomistic resolution privileging computational efficiency, can be used to characterize the dynamics of VLPs. Still, the massive amount of solvent present in empty capsids or envelopes suggests that hybrid schemes keeping a higher resolution on regions of interest (i.e., the viral proteins and their surroundings) and a progressively coarser description on the bulk may further improve efficiency. Here we introduce a mesoscale explicit water model to be used in double- or triple-scale simulations in combination with popular atomistic parameters and the CG water used by the SIRAH force field. Simulations performed on VLPs of different sizes, along with a comprehensive analysis of the PDB, indicate that most of the VLPs so far reported are amenable to be handled on a GPU-accelerated desktop computer using this simulation scheme.
病毒是极其高效的分子装置，它们使用最少数量的蛋白质来优化遗传物质的包装，形成保护自身免受外部威胁的衣壳或包膜，同时也是细胞识别、融合和出芽机制的一部分。实验技术的进步提供了大量病毒和类病毒颗粒（VLP）的高分辨率结构，而分子动力学模拟则可以为病毒组装、稳定性和动力学的基本力提供生动而互补的见解。然而，这些大分子组装体的巨大尺寸和复杂性带来了重大的计算挑战。或者，可以使用粗粒化（CG）方法来表征 VLP 的动力学，该方法放弃原子分辨率，以提高计算效率。尽管如此，空衣壳或包膜中存在大量溶剂表明，混合方案在保持更高分辨率的感兴趣区域（即病毒蛋白及其周围环境）的同时，对大部分区域进行逐渐更粗糙的描述，可能会进一步提高效率。在这里，我们引入了一种介观显式水分子模型，可用于与流行的原子参数和 SIRAH 力场使用的 CG 水结合的双或三尺度模拟。对不同大小的 VLP 进行的模拟以及对 PDB 的全面分析表明，迄今为止报道的大多数 VLP 都可以使用这种模拟方案在 GPU 加速的台式计算机上进行处理。
