Modeling Protonation Equilibria In Biological Macromolecules

  • Jana Khandogin
Part of the Challenges and Advances in Computational Chemistry and Physics book series (COCH, volume 7)


The stability and function of proteins are dependent on the charge states. For more than a decade, theoretical methods for the prediction of protonation equilibria in proteins have been based on a macroscopic description in which the dielectric response of protein to the fluctuating environment is modeled implicitly through an effective dielectric constant. Recently, constant pH molecular dynamics methods have been developed, which allow for an explicit coupling between the conformational dynamics and protonation equilibria in proteins. Of particular interest is the continuous constant pH method based on λ dynamics and GB implicit models. This method has enabled accurate and robust pK a predictions for proteins, and simulations of pH-coupled protein folding from first principles


Molecular dynamics pKa Protein folding pH-dependent conformational change 


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© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Department of Chemistry & BiochemistryUniversity of OklahomaNormanUSA

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