Exploring pH Dependent Host/Guest Binding Affinities.

ABSTRACT: When the electrostatic environment surrounding binding partners changes between unbound and bound states, the net uptake or release of a proton is possible by either binding partner. This process is pH-dependent in that the free energy required to uptake or release the proton varies with pH. This pH-dependence is typically not considered in conventional free energy methods where the use of fixed protonation states is the norm. In the present paper, we apply a simple two-step approach to calculate the pH-dependent binding free energy of a model cucubit[7]uril host/guest system. By use of λ-dynamics with an enhanced sampling protocol, adaptive landscape flattening, pK_a shifts and reference binding free energies upon complexation were determined. This information enables the

SUBMITTER: Paul TJ 

PROVIDER: S-EPMC7442968 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature