Department of Physics, Graduate School of Science, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan.
Komaba Organization for Educational Excellence, College of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan.
Molecules. 2022 Jul 12;27(14):4460. doi: 10.3390/molecules27144460.
Despite the recent advances in the prediction of protein structures by deep neutral networks, the elucidation of protein-folding mechanisms remains challenging. A promising theory for describing protein folding is a coarse-grained statistical mechanical model called the Wako-Saitô-Muñoz-Eaton (WSME) model. The model can calculate the free-energy landscapes of proteins based on a three-dimensional structure with low computational complexity, thereby providing a comprehensive understanding of the folding pathways and the structure and stability of the intermediates and transition states involved in the folding reaction. In this review, we summarize previous and recent studies on protein folding and dynamics performed using the WSME model and discuss future challenges and prospects. The WSME model successfully predicted the folding mechanisms of small single-domain proteins and the effects of amino-acid substitutions on protein stability and folding in a manner that was consistent with experimental results. Furthermore, extended versions of the WSME model were applied to predict the folding mechanisms of multi-domain proteins and the conformational changes associated with protein function. Thus, the WSME model may contribute significantly to solving the protein-folding problem and is expected to be useful for predicting protein folding, stability, and dynamics in basic research and in industrial and medical applications.
尽管最近在通过深度神经网络预测蛋白质结构方面取得了进展，但阐明蛋白质折叠机制仍然具有挑战性。一种描述蛋白质折叠的有前途的理论是一种称为 Wako-Saitô-Muñoz-Eaton (WSME) 模型的粗粒度统计力学模型。该模型可以根据低计算复杂度的三维结构计算蛋白质的自由能景观，从而全面了解折叠途径以及涉及折叠反应的中间体和过渡态的结构和稳定性。在这篇综述中，我们总结了使用 WSME 模型进行的蛋白质折叠和动力学的先前和最新研究，并讨论了未来的挑战和前景。WSME 模型成功地预测了小单域蛋白质的折叠机制以及氨基酸取代对蛋白质稳定性和折叠的影响，与实验结果一致。此外，WSME 模型的扩展版本被应用于预测多域蛋白质的折叠机制以及与蛋白质功能相关的构象变化。因此，WSME 模型可能对解决蛋白质折叠问题有重大贡献，并有望在基础研究以及工业和医疗应用中用于预测蛋白质折叠、稳定性和动力学。
