Klein Florencia, Soñora Martín, Helene Santos Lucianna, Nazareno Frigini Ezequiel, Ballesteros-Casallas Andrés, Rodrigo Machado Matías, Pantano Sergio
Laboratoire de Biochimie Théorique, UPR9080, CNRS, Paris, France.
Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay.
J Struct Biol. 2023 Sep;215(3):107985. doi: 10.1016/j.jsb.2023.107985. Epub 2023 Jun 16.
The different combinations of molecular dynamics simulations with coarse-grained representations have acquired considerable popularity among the scientific community. Especially in biocomputing, the significant speedup granted by simplified molecular models opened the possibility of increasing the diversity and complexity of macromolecular systems, providing realistic insights on large assemblies for more extended time windows. However, a holistic view of biological ensembles' structural and dynamic features requires a self-consistent force field, namely, a set of equations and parameters that describe the intra and intermolecular interactions among moieties of diverse chemical nature (i.e., nucleic and amino acids, lipids, solvent, ions, etc.). Nevertheless, examples of such force fields are scarce in the literature at the fully atomistic and coarse-grained levels. Moreover, the number of force fields capable of handling simultaneously different scales is restricted to a handful. Among those, the SIRAH force field, developed in our group, furnishes a set of topologies and tools that facilitate the setting up and running of molecular dynamics simulations at the coarse-grained and multiscale levels. SIRAH uses the same classical pairwise Hamiltonian function implemented in the most popular molecular dynamics software. In particular, it runs natively in AMBER and Gromacs engines, and porting it to other simulation packages is straightforward. This review describes the underlying philosophy behind the development of SIRAH over the years and across families of biological molecules, discussing current limitations and future implementations.
分子动力学模拟与粗粒度表示的不同组合在科学界颇受欢迎。特别是在生物计算领域，简化分子模型带来的显著加速使得增加大分子系统的多样性和复杂性成为可能，从而在更长的时间窗口内为大型组装体提供真实的见解。然而，要全面了解生物集合体的结构和动态特征，需要一个自洽的力场，即一组描述不同化学性质部分（即核酸和氨基酸、脂质、溶剂、离子等）之间分子内和分子间相互作用的方程和参数。尽管如此，在完全原子级和粗粒度水平的文献中，这种力场的例子很少。此外，能够同时处理不同尺度的力场数量有限。其中，我们团队开发的SIRAH力场提供了一组拓扑结构和工具，便于在粗粒度和多尺度水平上设置和运行分子动力学模拟。SIRAH使用与最流行的分子动力学软件中实现的相同经典成对哈密顿函数。特别是，它可以在AMBER和Gromacs引擎中原生运行，并且将其移植到其他模拟软件包很简单。这篇综述描述了多年来SIRAH在不同生物分子家族开发背后的基本理念，讨论了当前的局限性和未来的实现方式。
