Binding of Pollutants to Biomolecules: A Simulation Study

A number of cases around the world have been reported where animals were found dead or dying with symptoms resembling a thiamine (vitamin B) deficiency, and for some of these, a link to pollutants has been suggested. Here, we investigate whether biomolecules involved in thiamin binding and transport could be blocked by a range of different pollutants. We used in silico docking of five compound classes (25 compounds in total) to each of five targets (prion protein, ECF-type ABC transporter, thi-box riboswitch receptor, thiamin pyrophosphokinase, and YKoF protein) and subsequently performed molecular dynamics (MD) simulations to assess the stability of the complexes. The compound classes were thiamin analogues (control), pesticides, veterinary medicines, polychlorinated biphenyls, and dioxins, all of which are prevalent in the environment to some extent. A few anthropogenic compounds were found to bind the ECF-type ABC transporter, but none binds stably to prion protein. For the riboswitch, most compounds remained in their binding pockets during 50 ns of MD simulation, indicating that RNA provides a promiscuous binding site. In both YKoF and thiamin pyrophosphokinase (TPK), most compounds remain tightly bound. However, TPK biomolecules undergo pollutant-induced conformational changes. Although most compounds are found to bind to some of these targets, a larger data set is needed along with more quantitative methods like free energy perturbation calculations before firm conclusions can be drawn. This study is in part a test bed for large-scale quantitative computational screening of interactions between biological entities and pollutant molecules.