passages.id: split_4_validation_1226_passage
passages.type: progene_text
passages.text: However , as additional calculations for the monoprotonated complete complexes show a reduction in the energy differences between the neutral - pair keto and ion - pair keto ( N8 - or N5 - protonated ) forms , we are extending the treatment using combined quantum mechanics and molecular mechanics ( QM / MM ) and molecular dynamics simulation methods to refine the description of the protein / solvent environment and prediction of the relative stabilization free energies of the various ( OD2 , O4 , N5 , and N8 ) protonation sites .