Phosphorylation is one of the most frequent post-translational modifications on proteins. It regulates many cellular processes by modulation of phosphorylation on protein structure and dynamics. However, the mechanism of phosphorylation-induced conformational changes of proteins is still poorly understood. Here, we report a computational study of three representative groups of tyrosine in ADP-ribosylhydrolase 1, serine in BTG2, and serine in Sp100C by using six molecular dynamics (MD) simulations and quantum chemical calculations. Added phosphorylation was found to disrupt hydrogen bond, and increase new weak interactions (hydrogen bond and hydrophobic interaction) during MD simulations, leading to conformational changes. Quantum chemical calculations further indicate that the phosphorylation on tyrosine, threonine, and serine could decrease the optical band gap energy (Egap), which can trigger electronic transitions to form or disrupt interactions easily. Our results provide an atomic and electronic description of how phosphorylation facilitates conformational and dynamic changes in proteins, which may be useful for studying protein function and protein design.