Relationships between hydrogen bonds and halogen bonds in biomolecular engineering

2019 Fall.Includes bibliographical references.In this dissertation, we will explore the interconnectedness between halogen bonds (X-bonds) and hydrogen bonds in rational biomolecular engineering efforts. As X-bonds are not readily designed into biomolecules, we aim to show how they can be advantageous for molecular design. We will begin by considering how X-bonds compare to H-bonds and show how the two can work in harmony to provide enhanced stabilizing potential. In two unique protein engineering efforts we will show 1) how the X-bond can be just as specifying in terms of molecular assembly as compared to the H-bond, and 2) how it can coordinate with the H-bond to increase protein stability. One study shows the specifying potential the X-bond possesses in terms of coiled-coil assembly. While the study points to a direct application of a sensing probe, the scope of the work will aid others using coiled-coils for materials purpose, designing protein interfaces or potential ligand binding sites. In the other protein engineering study, we will survey how a protein with an intrinsically disordered region responds to hydrogen enhanced halogen bond engineering. We show how we can drastically increase the thermal stability of the protein through minimal change to its primary sequence. This study lends itself to exploring bigger structure-function questions and how the stabilizing capacity of halogen bonds fits into this. Through this work we aspire to show how useful X-bonds can be for biological engineering efforts by exhibiting their specifying and stabilizing characteristics in these settings