Biomolecular recognition usually leads to the formation of binding complexes, often accompanied by large-scale conformational changes. This process is fundamental to biological functions at the molecular and cellular levels. Uncovering the physical mechanisms of biomolecular recognition and quantifying the key biomolecular interactions are vital to understand these functions. The recently developed energy landscape theory has been successful in quantifying recognition processes and revealing the underlying mechanisms. Recent studies have shown that in addition to affinity, specificity is also crucial for biomolecular recognition. The proposed physical concept of intrinsic specificity based on the underlying energy landscape theory provides a practical way to quantify the specificity. Optimization of affinity and specificity can be adopted as a principle to guide the evolution and design of molecular recognition. This approach can also be used in practice for drug discovery using multidimensional screening to identify lead compounds. The energy landscape topography of molecular recognition is important for revealing the underlying flexible binding or binding–folding mechanisms. In this review, we first introduce the energy landscape theory for molecular recognition and then address four critical issues related to biomolecular recognition and conformational dynamics: (1) specificity quantification of molecular recognition; (2) evolution and design in molecular recognition; (3) flexible molecular recognition; (4) chromosome structural dynamics. The results described here and the discussions of the insights gained from the energy landscape topography can provide valuable guidance for further computational and experimental investigations of biomolecular recognition and conformational dynamics.

中文翻译：

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生物分子识别和构象动力学物理学

生物分子识别通常导致结合复合物的形成，通常伴随着大规模的构象变化。这个过程是分子和细胞水平的生物学功能的基础。揭示生物分子识别的物理机制和量化关键的生物分子相互作用对于理解这些功能至关重要。最近发展起来的能源景观理论在量化识别过程和揭示潜在机制方面取得了成功。最近的研究表明，除了亲和力外，特异性对于生物分子识别也至关重要。基于潜在的能量景观理论提出的内在特异性的物理概念提供了一种量化特异性的实用方法。亲和力和特异性的优化可以作为指导分子识别进化和设计的原则。这种方法也可以在实践中用于药物发现，使用多维筛选来识别先导化合物。分子识别的能量图谱对于揭示潜在的柔性结合或结合折叠机制很重要。在这篇综述中，我们首先介绍了分子识别的能量景观理论，然后解决了与生物分子识别和构象动力学相关的四个关键问题：（1）分子识别的特异性量化；(2) 分子识别的进化与设计；(3) 灵活的分子识别；(4)染色体结构动力学。