PhD Defence | Unravelling protein sequence specificity: a functional and structural perspective
Vrije Universiteit Amsterdam PhD candidate, Maurits Dijkstra will be defending his PhD thesis “Unravelling protein sequence specificity: a functional and structural perspective” on Thursday 7th January.
Maurits Dijkstra’s thesis investigates the relationship between the amino acid sequence of a protein and its properties. Maurits completed his research under the supervision of Jaap Heringa, Sanne Abeln and Wan Fokkink (all from VU Amsterdam).
In an organism, proteins drive the majority of processes, including the catalysis of chemical reactions, the transport of molecules and signals, and the replication of the genomic code. Invariably, biological studies involve investigating the properties of one or more proteins. A protein is made up of building blocks called amino acids. Amino acids come in different types, and the order in which they appear in a protein determines its sequence.
The majority of a protein’s properties are derived from the interplay between the different physicochemical properties of its amino acids, and between its amino acids and the water molecules surrounding them. These effects are responsible for allowing a protein to take its macroscopic shape, through a process called protein folding. They also enable more localized, functional properties, such as signal recognition and catalysis by motifs, or small arrangements of amino acids of specific types.
In his thesis, Maurits presents MA-PRALINE, a sequence analysis program that is better able to analyze proteins containing motifs. The algorithm behind MA-PRALINE is also employed in ConBind, another sequence analysis program, which is used to study the molecular switches in DNA that turn proteins on and off. To study the role the sequence plays in the formation of intermediate molten globules during protein folding, an existing lattice model simulation is adapted. By fixing the desired conformation, but varying the sequence, it is shown that it is possible to influence the way a protein folds, without impacting its functional shape.