Computational study of the effect of protonation states of PSA protein zinc fingers on its DNA binding

Abstract

In this study, we investigate the binding of the Zinc finger (ZF) structure on a short DNA molecule. The zinc finger of a protein where a Zn2+ ion binds to 4 cysteine or histidine amino acids in a tetrahedral structure is a very common motif of nucleic acid binding proteins. This structure is ubiquitous and the corresponding interaction model is present in 3% of the genes of human genome. ZF has been shown to be extremely useful in various therapeutic and research capacities, as well as in biotechnology. A recent computational study has shown that isolated zinc finger structure is stable if the cysteine amino acids are in deprotonated state. Here, we investigate how this deprotonated state influences protein structure, dynamics, and function in binding of ZF to short DNA molecules using molecular dynamics simulations in sub-microsecond range. Our results show that the Zn2+ ion and the deprotonated state of cysteine is essential for mechanical stabilization of the functional, folded conformation. Not only this state stabilizes the ZF structure, it also stabilizes the DNA-binding structure. Our result has potential impact on better design of zinc fingers for various biotechnological applications.