Extending the Martini Coarse-Grained Force Field to N-Glycans.,Journal of Chemical Information and Modeling

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Extending the Martini Coarse-Grained Force Field to N-Glycans.
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2020-07-06 , DOI: 10.1021/acs.jcim.0c00495
Aishwary T Shivgan _{1,

2} , Jan K Marzinek ₂ , Roland G Huber ₂ , Alexander Krah ₂ , Richard H Henchman _{3,

4} , Paul Matsudaira _{1,

5} , Chandra S Verma _{1,

2,

6} , Peter J Bond _{1,

2}

Affiliation

Glycans play a vital role in a large number of cellular processes. Their complex and flexible nature hampers structure–function studies using experimental techniques. Molecular dynamics (MD) simulations can help in understanding dynamic aspects of glycans if the force field parameters used can reproduce key experimentally observed properties. Here, we present optimized coarse-grained (CG) Martini force field parameters for N-glycans, calibrated against experimentally derived binding affinities for lectins. The CG bonded parameters were obtained from atomistic (ATM) simulations for different glycan topologies including high mannose and complex glycans with various branching patterns. In the CG model, additional elastic networks are shown to improve maintenance of the overall conformational distribution. Solvation free energies and octanol–water partition coefficients were also calculated for various N-glycan disaccharide combinations. When using standard Martini nonbonded parameters, we observed that glycans spontaneously aggregated in the solution and required down-scaling of their interactions for reproduction of ATM model radial distribution functions. We also optimized the nonbonded interactions for glycans interacting with seven lectin candidates and show that a relatively modest scaling down of the glycan-protein interactions can reproduce free energies obtained from experimental studies. These parameters should be of use in studying the role of glycans in various glycoproteins and carbohydrate binding proteins as well as their complexes, while benefiting from the efficiency of CG sampling.

中文翻译：

将马提尼粗粒力场扩展到N-糖浆。

聚糖在许多细胞过程中起着至关重要的作用。它们复杂而灵活的性质阻碍了使用实验技术进行结构功能研究。如果使用的力场参数可以重现关键的实验观察特性，则分子动力学（MD）模拟可以帮助理解聚糖的动力学方面。在这里，我们为N提供了优化的粗粒（CG）马提尼力场参数-聚糖，针对凝集素的实验衍生结合亲和力进行了校准。CG键合参数是从原子（ATM）模拟获得的，用于不同的聚糖拓扑结构，包括高甘露糖和具有各种分支模式的复杂聚糖。在CG模型中，显示了其他弹性网络以改善总体构象分布的维护。还计算了各种氮的溶剂化自由能和辛醇-水分配系数-聚糖二糖组合。当使用标准马提尼酒非结合参数时，我们观察到聚糖自发地聚集在溶液中，并且需要按比例缩小它们的相互作用以再现ATM模型的径向分布函数。我们还优化了与七个凝集素候选物相互作用的聚糖的非键相互作用，并显示相对适度的聚糖-蛋白相互作用的缩减可以重现从实验研究中获得的自由能。这些参数应用于研究聚糖在各种糖蛋白和碳水化合物结合蛋白及其复合物中的作用，同时受益于CG采样的效率。

更新日期：2020-08-24

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