Nuclear magnetic resonance (NMR) spectroscopy has contributed to structure-based drug development (SBDD) in a unique way compared to the other biophysical methods. The potency of a ligand binding to a protein is dictated by the binding free energy, which is an intricate interplay between entropy and enthalpy. In addition to providing the atomic resolution structural information, NMR can help to identify protein–ligand interactions that potentially contribute to the enthalpic component of the free energy. NMR can also illuminate dynamic aspects of the interaction, which correspond to the entropic term of the free energy. The ability of NMR to access both terms in the free energy equation stems from the suite of experiments developed to shed light on various aspects that contribute to both entropy and enthalpy, deepening our understanding of the biological function of macromolecules and assisting to target them in physiological conditions. Here we provide a brief account of the contribution of NMR to SBDD, highlighting hallmark examples and discussing the challenges that demand further method development. In the era of integrated biology, the unique ability of NMR to directly ascertain structural and dynamical aspects of macromolecule and monitor changes in these properties upon engaging a ligand can be combined with computational and other structural and biophysical methods to provide a more complete picture of the energetics of drug engagement with the target. Such efforts can be used to engineer better drugs.

与其他生物物理方法相比，核磁共振（NMR）波谱以独特的方式为基于结构的药物开发（SBDD）做出了贡献。配体与蛋白质结合的效力由结合自由能决定，结合自由能是熵和焓之间复杂的相互作用。除了提供原子分辨率的结构信息外，核磁共振还可以帮助识别蛋白质-配体相互作用，这些相互作用可能有助于自由能的焓部分。核磁共振还可以阐明相互作用的动态方面，这对应于自由能的熵项。核磁共振获取自由能方程中这两项的能力源于一系列实验，这些实验旨在阐明促成熵和焓的各个方面，加深我们对大分子生物学功能的理解，并帮助在生理学中靶向它们。状况。在这里，我们简要介绍了 NMR 对 SBDD 的贡献，重点介绍了标志性示例并讨论了需要进一步开发方法的挑战。在整合生物学时代，核磁共振具有直接确定大分子的结构和动力学方面并监测配体参与后这些性质变化的独特能力，可以与计算和其他结构和生物物理方法相结合，以提供更完整的图像。药物与靶标结合的能量学。这些努力可用于设计更好的药物。