We introduce the fragment‐pairwise Local Energy Decomposition (fp‐LED) scheme for precise quantification of individual interactions contributing to the binding energy of arbitrary chemical entities, such as protein‐ligand binding energies, lattice energies of molecular crystals, or association energies of large biomolecular assemblies. Using fp‐LED, we can assess whether the contribution to the binding energy arising from noncovalent interactions between pairs of molecular fragments in any chemical system is attractive or repulsive, and accurately quantify its magnitude at the coupled cluster level ‐ commonly considered as the “gold standard” of computational chemistry. Such insights are crucial for advancing molecular and material design strategies in fields like catalysis and therapeutic development. Illustrative applications across diverse fields demonstrate the versatility and accuracy of this theoretical framework, promising profound implications for fundamental understanding and practical applications.

中文翻译：

---

一种普遍适用的方法，用于解开单个非共价相互作用对结合能的影响


我们引入了片段成对局部能量分解 （fp-LED） 方案，用于精确量化导致任意化学实体结合能的单个相互作用，例如蛋白质-配体结合能、分子晶体的晶格能或大型生物分子组装体的缔合能。使用 fp-LED，我们可以评估任何化学系统中分子片段对之间的非共价相互作用对结合能的贡献是有吸引力的还是排斥的，并在耦合簇水平上准确量化其大小——这通常被认为是计算化学的“黄金标准”。这些见解对于推进催化和治疗开发等领域的分子和材料设计策略至关重要。不同领域的说明性应用证明了这一理论框架的多功能性和准确性，有望对基本理解和实际应用产生深远影响。