A fully atomistic (AT) modeling of biological macromolecules at relevant length‐ and time‐scales is often cumbersome or not even desirable, both in terms of computational effort required and a posteriori analysis. This difficulty can be overcome with the use of multiresolution models, in which different regions of the same system are concurrently described at different levels of detail. In enzymes, computationally expensive AT detail is crucial in the modeling of the active site in order to capture, for example, the chemically subtle process of ligand binding. In contrast, important yet more collective properties of the remainder of the protein can be reproduced with a coarser description. In the present work, we demonstrate the effectiveness of this approach through the calculation of the binding free energy of hen egg white lysozyme with the inhibitor di‐N‐acetylchitotriose. Particular attention is payed to the impact of the mapping, that is, the selection of AT and coarse‐grained residues, on the binding free energy. It is shown that, in spite of small variations of the binding free energy with respect to the active site resolution, the separate contributions coming from different energetic terms (such as electrostatic and van der Waals interactions) manifest a stronger dependence on the mapping, thus pointing to the existence of an optimal level of intermediate resolution.

中文翻译：

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通过双分辨率模型研究溶菌酶中的配体-蛋白质相互作用。

在所需的计算工作量和后验分析方面，在相关的长度和时间尺度上对生物大分子进行完全原子（AT）建模通常很麻烦，甚至不希望这样做。使用多分辨率模型可以克服此困难，在该模型中，同时以不同的详细程度描述同一系统的不同区域。在酶中，为了捕获例如配体结合的化学微妙过程，计算上昂贵的AT细节对于活性位点的建模至关重要。相反，可以用较粗略的描述来再现蛋白质其余部分的重要而更集体的性质。在目前的工作中，我们通过计算鸡蛋清溶菌酶与抑制剂di-N-乙酰壳聚糖三糖的结合自由能来证明这种方法的有效性。特别要注意映射的影响，即AT和粗粒残基的选择对结合自由能的影响。结果表明，尽管结合自由能相对于活性位点分辨率有很小的变化，但是来自不同能量项（例如静电和范德华相互作用）的单独贡献显示出对映射的较强依赖性，因此指出存在最佳水平的中间分辨率。