Novel Approach for Characterizing Propofol Binding Affinities to Serum Albumins from Different Species

The
interaction between the main carrier (serum albumin, SA) of
endogenous and exogenous compounds in the bloodstream of different
species (human, bovine, canine, rat, rabbit, and sheep) and a general
anesthetic agent (propofol, PR) was investigated using an experimental
technique (high-performance liquid chromatography) and computational
methods (molecular docking, molecular dynamics, sequence, and phylogenetic
analyses). The obtained results revealed the differences in the PR
binding affinity to various homologous forms of this protein with
reliable statistics (R2 = 0.9 and p-value < 0.005), correlating with the evolutionary relationships
among SAs from different species. Additionally, the protein conformational
changes (root-mean-square deviation ≈ 1.0 Å) and amino
acid conservation of binding sites in protein domains were detected,
contributing to the SA–PR binding modes. Overall, the outcomes
from this study might provide a novel methodology to assess protein–ligand
interactions and to gain some interesting insights into drug pharmacokinetics
and pharmacodynamics to explain its variations among different species.