Computationally driven material design has attracted increasing interest to accelerate the search for optimal conjugated donor materials in bulk heterojunction organic solar cells. A series of novel copolymers containing benzo[1,2-b:4,5-b']dithiophene (BDT) and thieno[3,4-c]pyrrole-4,6-dione (TPD) derivatives were simulated by density functional theory (DFT) and time-dependent density functional theory (TD-DFT). We performed a systematic study on the influences on molecular geometry parameters, electronic properties, optical properties, photovoltaic performances, and intermolecular stacking as well as hole mobility when different chalcogenophenes in TPD derivatives were used and functional groups with different electron-withdrawing abilities such as alkyl, fluorine, sufonyl, and cyano were introduced to the nitrogen positions in electron-deficient units. The substitution position of electron-withdrawing groups may cause little steric hindrance to the neighboring donor units, especially fluorine and cyano group. It was found that the incorporation of these new electron-deficient substituents and sulfur-selenium exchange can be applicable to further modify and optimize existing molecular structures. Our findings will provide valuable guidance and chemical methodologies for a judicious material design of conjugated polymers for solar cell applications with desirable photovoltaic characteristics.