In conclusion, we have reported the virtual ligand-assisted optimization (VLAO) method, a rational strategy for ligand engineering. In this method, the electronic and steric effects of phosphine ligands on the reaction outcome can be mathematically quantified by differentiating energies of equilibrium structures and transition states in terms of electronic and steric parameters in the virtual ligand. The obtained derivative values can be used as a rational principle of ligand optimization. Indeed, the VLAO method reproduced reported design for monodentate, bidentate and asymmetric phosphine ligands. In addition, an optimal ligand for the α-selective hydrogermylation of terminal ynamide 9b was rapidly designed and discovered based on the guiding principle by the VLAO method.