In this talk,I will present our recent progresses in developing electronic structure methods for large systems and provide some interesting applications of these methods.The approach we developed is the generalized energy-based fragmentation (GEBF) approach,in which the ground-state energy (or various properties) of a large molecule can be extracted directly from energies (or properties) of various “embedded” subsystems.[1,2] The GEBF approach can be used to obtain relative energies of different conformers,optimized structures,vibrational frequencies and intensities,and some molecular properties for large molecules or molecular clusters.[3-5].