Computational investigations of B₁₂-dependent enzymatic reactions

Nature employs two biologically active forms of vitamin B₁₂, adenosylcobalamin (or coenzyme B₁₂) and methylcobalamin, as cofactors in molecular transformations both in bacteria and mammals. Computational chemistry, guided by experimental data, has been used to explore fundamental characteristics of these enzymatic reactions. In particular, the quantum mechanics/molecular mechanics (QM/MM) method has proven to be a powerful tool in elucidating important characteristics of B₁₂-dependent enzymatic reactions. Herein, we will present a brief tutorial in conducting QM/MM calculations for B₁₂ enzymatic reactions. We will summarize recent contributions that target the use of QM/MM calculations in both photochemical and enzymatic reactions including AdoCbl-dependent ethanolamine ammonia lyase, glutamate mutase, and photoreceptor CarH.