Presentation Title

Computationally Modeling Cys-Lite Variants of Haspin Kinase

Abstract

The Haspin protein kinase is unique due to its abnormal structural features assisting in stabilizing the active site of the protein. Without Haspin kinase, the chromosomes in mitosis can prematurely split and the metaphase chromosomes can misalign causing mitotic arrest. In this research, a computational study was performed in which a variety of programs were used to predict whether the protein would become more or less active due to eight mutations. The structure of Haspin was mutated using PYMOL and minimized using RefineD and MolProbity. Based on these computational studies, we predict that point mutations C478A, C487A, C564S, C679S, and C792S would not significantly affect Haspin structure or function. However, in minimized structures with mutations C550S, C702S, and C762S, some parts of the protein were misaligned with the wildtype structure. We therefore predict that their conformation and function may be somewhat different from the wild-type Haspin. Changes in pKa values for some residues were also predicted using the program H++.

College

College of Science & Engineering

Department

Chemistry

Location

Winona, Minnesota

Breakout Room

34

Start Date

4-14-2021 2:00 PM

End Date

4-14-2021 2:45 PM

Presentation Type

Video (Live-Zoom)

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Apr 14th, 2:00 PM Apr 14th, 2:45 PM

Computationally Modeling Cys-Lite Variants of Haspin Kinase

Winona, Minnesota

The Haspin protein kinase is unique due to its abnormal structural features assisting in stabilizing the active site of the protein. Without Haspin kinase, the chromosomes in mitosis can prematurely split and the metaphase chromosomes can misalign causing mitotic arrest. In this research, a computational study was performed in which a variety of programs were used to predict whether the protein would become more or less active due to eight mutations. The structure of Haspin was mutated using PYMOL and minimized using RefineD and MolProbity. Based on these computational studies, we predict that point mutations C478A, C487A, C564S, C679S, and C792S would not significantly affect Haspin structure or function. However, in minimized structures with mutations C550S, C702S, and C762S, some parts of the protein were misaligned with the wildtype structure. We therefore predict that their conformation and function may be somewhat different from the wild-type Haspin. Changes in pKa values for some residues were also predicted using the program H++.