The present work consists of the development of a new model (named "one-into-many") to predict the regioselectivity of large chemical and biological systems. Large chemical and biological systems with multiple reactive sites are proposed to be broken into small fragments having at least one reactive site in each fragment. The environment around each reactive site is mimicked by incorporating a buffer zone. Local reactivity descriptor (i.e., local hardness), originally proposed by Berkowitz et al. (J. Am. Chem. Soc. 1985, 107, 6811) and later implemented by Langenaeker et al. (J. Phys. Chem. 1995, 99, 6424), is evaluated for each reactive site adopting a new modified approach (i.e., without neglecting kinetic energy and exchange energy parts). When the model is applied to predict the regioselectivity (toward an electrophilic attack) of the base pairs in DNA (PDB ID: 1BNA) (Proc. Natl. Acad. Sci. U.S.A. 1981, 78, 2179) the generated results are found to be satisfactory in most cases.