We have evaluated the strength of intramolecular hydrogen bond in a protein based on molecular dynamics and quantum chemical calculation. To estimate the intramolecular hydrogen bond strength in okadaic acid (OA), we analyzed the influence of solvent and protonation states on the hydrogen bond and the entire structure. We performed molecular dynamics calculation and analyzed the strength of the hydrogen bond by measuring bond length and bond angle. The stable structure differs depending on the kind of solvent used and the protonation state of OA. Using the mean interaction energy from the quantum chemical calculation, hydrogen bond length and angle were investigated against bond energy. Although dielectric constant slightly depends on bond energy, the estimation of the intramolecular hydrogen bond strength in OA is possible even in a protein environment. The Coulomb interaction between OA and surrounding arginine produced a more negatively charged O1 in OA. The hydrogen bond energy in the deprotonated state is larger than that in the protonated state.