Role of the Protonation State on the Structure and Dynamics of Albumin

Human
serum albumin undergoes reversible conformational transitions
associated with ligand binding or pH changes. Among them, the neutral
to base (N → B) transition
occurring between pH 7 and pH 9 seems to be relevant for its function
as a carrier. Unfortunately, a detailed atomic model for the B-form is still lacking, and several open questions remain
concerning the charge distribution of the N-form.
In this work, we report comparable molecular models for the N and B conformations that are built using
continuum electrostatic calculations of pKa values and extended molecular dynamics (MD) simulations. Our computational
models, which are critically assessed in terms of the available experimental
observations relative to the N → B transition, reveal interesting similarities and differences between
the N- and B-forms of HSA and highlight
the importance of setting proper charge configurations in MD simulations.