CE Seminar by Dr. Ayşegül Turupçu – Molecular simulations of glycans and glycoproteins with combined NMR/MD approaches

February 17, 2020






Speaker: Dr. Ayşegül Turupçu, Postdoctoral Research Associate at Yale University

Title: Molecular simulations of glycans and glycoproteins with combined NMR/MD approaches

Date: Tuesday, February 18, 2020

Time: 15:30

Place: ENG 208



With the development of protein-based drugs, glycoproteins have become increasingly used in the therapeutic area. Its ability to increase protein molecular stability, specificity, activity and change the protein properties made glycosylation very popular. The attached carbohydrate units, glycans, affect various properties of proteins; e.g. stability, activity, and immunogenicity. Biological functions of the glycans benefited from the design of specific monoclonal antibodies, e.g. for HIV vaccine development. However, the inherent complexity of glycosylation forms a challenge both for experimental and theoretical methods. There is a pronounced lack of 3D conformational information, obscuring the whole picture about their biological functions.

In this context, the solution conformations of all disaccharides constituting biologically relevant N- and O-linked glycan units are studied using the local elevation umbrella sampling method (LEUS). The adaptable nature of the LEUS method allows modeling of the carbohydrate moiety of the glycoproteins by using biasing potentials for glycosidic linkages of all disaccharide fragments in the glycan unit and enhancing the sampling in the production phase. I followed a bottom up approach by increasing complexity from disaccharide level to higher oligosaccharide level. This allowed me to use several efficient methods to model the glycoprotein in the absence of any experimental data. Examples will be presented from important monoclonal antibodies; e.g. IgA, IgG and IgE as well as complex lambda lysozyme protein dynamics from combined NMR/computational approaches.



Aysegul Turupcu is currently a postdoctoral associate at Yale University, in the Chemistry Department. She is working on parametrization of the OPLS force field at the Prof. William Jorgensen Lab. She performed her Ph.D. thesis under the supervision of Prof. Chris Oostenbrink in Austria where she implemented a workflow for modeling the glycoprotein in the absence of any experimental data and contributed GROMOS molecular dynamics (MD) software. She published interdisciplinary works where she applied multiple free-energy calculation techniques (TI, OSP, EDS) and enhanced sampling methods (LEUS, metadynamics) in the areas of vaccine development, antibody and specific antibacterial design as well as carbohydrate conformation. She worked at Oxford University as a visiting researcher and gained expertise in combining solution-state nuclear magnetic resonance (NMR) data with MD simulation in the study of protein dynamics.