论文标题
蛋白质的快速，准确和系统特异性的可变分辨率建模
Fast, accurate, and system-specific variable-resolution modelling of proteins
论文作者
论文摘要
近年来，已经提出了一些多分辨率建模策略，其中用原子分辨率描述了生物分子的功能相关部分，而系统的其余部分则使用粗粒模型同时处理。在大多数情况下，后者的参数化需要冗长的参考全原子模拟和/或使用外架粗粒力场的使用，其相互作用必须完善以适合正在检查的特定系统。在这里，我们通过针对蛋白质的新型多分辨率建模方案克服了这些局限性，该模型称为可变分辨率模拟或画布的粗粒粒度各向异性网络模型。该方案可以在整个系统结构中对分辨率级别的用户定义调制；电势的快速参数化，无需参考模拟；该模型在最常用的分子动力学平台上的直接用法。该方法通过两种案例研究（腺苷酸酶激酶和治疗性抗体pembrolizumab）进行了验证，并通过将用画布模型与完全原子模拟进行比较，从而进行了治疗抗体pembrolizumab。在Python实施的建模软件可在协作GITHUB存储库中自由使用。
In recent years, a few multiple-resolution modelling strategies have been proposed, in which functionally relevant parts of a biomolecule are described with atomistic resolution, while the remainder of the system is concurrently treated using a coarse-grained model. In most cases, the parametrisation of the latter requires lengthy reference all-atom simulations and/or the usage of off-shelf coarse-grained force fields, whose interactions have to be refined to fit the specific system under examination. Here, we overcome these limitations through a novel multi-resolution modelling scheme for proteins, dubbed coarse-grained anisotropic network model for variable resolution simulations, or CANVAS. This scheme enables the user-defined modulation of the resolution level throughout the system structure; a fast parametrisation of the potential without the necessity of reference simulations; and the straightforward usage of the model on the most commonly used molecular dynamics platforms. The method is presented and validated on two case studies, the enzyme adenylate kinase and the therapeutic antibody pembrolizumab, by comparing results obtained with the CANVAS model against fully atomistic simulations. The modelling software, implemented in python, is made freely available for the community on a collaborative github repository.
