We explore the question of what are the best ligands for macromolecular targets. A survey of experimental data on a large number of the strongest-binding ligands indicates that the free energy of binding increases with the number of nonhydrogen atoms with an initial slope of ≈-1.5 kcal/mol (1 cal = 4.18 J) per atom. For ligands that contain more than 15 nonhydrogen atoms, the free energy of binding increases very little with relative molecular mass. This nonlinearity is largely ascribed to nonthermodynamic factors. An analysis of the dominant interactions suggests that van der Waals interactions and hydrophobic effects provide a reasonable basis for understanding binding affinities across the entire set of ligands. Interesting outliers that bind unusually strongly on a per atom basis include metal ions, covalently attached ligands, and a few well known complexes such as biotin-avidin.
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机译：我们探索什么是大分子目标的最佳配体的问题。对大量最强结合配体的实验数据的调查表明，结合的自由能随非氢原子数的增加而增加，每个原子的初始斜率约为≈-1.5kcal / mol（1 cal = 4.18 J）。对于含有超过15个非氢原子的配体，结合的自由能随相对分子质量的增加很少。这种非线性很大程度上归因于非热力学因素。对主要相互作用的分析表明，范德华相互作用和疏水作用为理解整个配体集的结合亲和力提供了合理的基础。在每个原子的基础上异常牢固结合的有趣异常值包括金属离子，共价连接的配体以及一些众所周知的复合物，例如生物素-亲和素。
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