There are several topics available in my group for students to work on, for a bachelor project, a master project or an extra project in the summer. You can find a list of available projects on the website of the Computational Chemistry group. Also, you can contact me directly: J.Vreede@uva.nl

Modeling the structure and formation of an H-NS DNA complex

The Histone-like Nucleoid Structuring protein (H-NS) is a small protein that organizes chromosomal DNA in bacteria, such as E. coli, salmonella and cholera. H-NS contains two dimerization sites and a DNA binding domain and it is dimeric in solution. By forming long filaments along double stranded DNA it bridges distinct regions of DNA. External factors, such as temperature, type and concentration of ions and the presence of helper proteins, influence the nature of such nucleoprotein complexes. The aim of these research projects is to develop structural models of H-NS - DNA complexes using molecular simulation approaches.  

Construct nucleoprotein filaments

For H-NS the structure of several fragments have been elucidated by crystallography, NMR and molecular dynamics simulations. These fragments can be combined into a larger structure using a Metropolis Monte Carlo approach, which allows for the investigation of the effect of nucleotide sequence, protein conformation and helper proteins. The project will consist of developing the Metropolis Monte Carlo approach for the H-NS DNA system, and investigating various conditions.

(6-9 month project)  

Modeling the formation of coiled coil complexes

Coiled coils are widely occurring protein interaction motifs that provide a stable scaffold for various protein functions. Comprising two to seven amphipathic α-helices wound into a supercoil, these systems rigidify protein complexes and regulate function through binding. Coiled coils stabilize multi-domain proteins and protein complexes,  and they govern protein activity by regulation through binding. The leucine zipper domain in the yeast transcription factor GCN4 dimerizes into a coiled coil, thus enabling DNA binding. Comprising two peptide chains, this complex rapidly folds into a supercoil. In a supercoil complex, the helices typically have a rise of seven residues per two turns, exhibiting a pattern of hydrophobic and hydrophilic residues, known as the heptad repeat. These residues tune the specificity of the coiled coil peptides as well as their preferred oligomeric state. A wealth of information is available on the effects of altering the heptad repeat sequence, facilitating structural prediction of supercoil complexes and de novo protein design. Nevertheless, the dynamics and mechanism of the formation and functioning of these coiled coil complexes are far from understood. In this project enhanced sampling methods such as metadynamics and transition path sampling will be used to compute the mechanisms and free energies associated with the formation of a coiled coil complex. 

(6-9 month project)