Quantitative structure‐activity relationship (QSAR) analysis has become one of the most effective approaches for optimizing lead compounds and designing new drugs. Although large number of quantum‐chemical descriptors were defined and applied successfully, it is still a big challenge to develop a general quantum‐chemical descriptor describing the bulk effects more directly and effectively. In this article, we defined a general quantum‐chemical descriptor by characterizing the volume of electron cloud for specific substituent using the metho...