To function, biomolecules require sufficient specificity of interaction as well as stability to live in the cell while still being able to move. Thermodynamic stability of only a limited number of specific structures is important so as to prevent promiscuous interactions. The individual interactions in proteins, therefore, have evolved collectively to give funneled minimally frustrated landscapes but some strategic parts of biomolecular sequences located at specific sites in the structure have been selected to be frustrated in order to allow both motion and interaction with partners. We describe a framework efficiently to quantify and localize biomolecular frustration at atomic resolution by examining the statistics of the energy changes that occur when the local environment of a site is changed. The location of patches of highly frustrated interactions correlates with key biological locations needed for physiological function. At atomic resolution, it becomes possible to extend frustration analysis to protein-ligand complexes. At this resolution one sees that drug specificity is correlated with there being a minimally frustrated binding pocket leading to a funneled binding landscape. Atomistic frustration analysis provides a route for screening for more specific compounds for drug discovery.

为了发挥功能，生物分子需要足够的相互作用特异性以及在细胞中仍然能够移动的稳定性。仅有限数量的特定结构的热力学稳定性是重要的，以防止混杂的相互作用。因此，蛋白质中的个体相互作用已经共同发展，从而产生了漏斗形的，最小的受挫景观，但是位于结构中特定位置的生物分子序列的某些战略性部分已被选择为受挫，以便允许运动以及与伴侣的相互作用。我们通过检查当站点的本地环境发生变化时发生的能量变化的统计数据，来描述一种以原子分辨率有效地量化和定位生物分子挫败的框架。高度挫败的相互作用的补丁的位置与生理功能所需的关键生物学位置相关。在原子分辨率下，将挫折分析扩展到蛋​​白质-配体复合物成为可能。在这种分辨率下，人们看到药物特异性与存在最小受挫的结合袋相关，从而导致了漏斗状结合态势。原子挫折分析提供了一种筛选用于药物发现的更具体化合物的途径。