Determinants of Plasma Protein Binding - an in silico study
Presented by Dr Nazanin Golbamaki at the UKQSAR Autumn Meeting, 2017.
Plasma protein binding (PPB) plays a crucial role in the dynamics of chemical interactions in vivo since it is the free (unbound) fraction that interacts with biomolecules, whereas the bound fraction is generally unable to cross cellular membranes, interact with molecular targets or undergo biotransformation.
Proteins are made up of amino acids, which contain positively charged amino groups and negatively charged carboxyl groups. There are two types of binding that can occur: reversible (hydrogen bonds, ionic bonds, Van der Waals forces) and irreversible (covalent bonds), with the latter demonstrating the greater potential to lead to adverse effects.
The main plasma proteins to which chemicals bind are human serum albumin (HSA), a-acid glycoprotein (AGP), and lipoproteins. Acidic and neutral compounds have higher affinity for HSA whilst basic substances bind primarily to AGP.
This study focuses on Quantitative Structure-Activity Relationships (QSAR) for the prediction of PPB where the effects of several chemical properties on the PPB was investigated, with a focus on the formal charge states.