Modelling flexible protein-ligand binding in p38α MAP kinase using the QUBE force field
Modelling flexible protein-ligand binding in p38α MAP kinase using the QUBE force field
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DOI：
10.1039/c9cc08574b
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发表时间：
2020-01-18
影响因子：
4.9
通讯作者：
Cole, Daniel J.
中科院分区：
文献类型：
--
作者：
Horton, Joshua T.;Allen, Alice E. A.;Cole, Daniel J.
量子力学定制（QUBE）力场被用来回顾性地计算一系列的17个灵活的p38 α MAP激酶抑制剂的相对结合自由能。所选分子的大小和灵活性代表了从量子力学推导力场参数的严格测试，并且需要增强采样以减少结果对起始结构的依赖性。实现了与广泛使用的生物力场的竞争准确性，表明量子力学导出的力场正在接近为前瞻性药物发现活动提供指导所需的准确性。
The quantum mechanical bespoke (QUBE) force field is used to retrospectively calculate the relative binding free energies of a series of 17 flexible inhibitors of p38 alpha MAP kinase. The size and flexibility of the chosen molecules represent a stringent test of the derivation of force field parameters from quantum mechanics, and enhanced sampling is required to reduce the dependence of the results on the starting structure. Competitive accuracy with a widely-used biological force field is achieved, indicating that quantum mechanics derived force fields are approaching the accuracy required to provide guidance in prospective drug discovery campaigns.