Peter Bolhuis

Peter Bolhuis

Understanding the mechanism of conformational change in T4-Lysozyme

Project type and duration:

3-6 months


Peter Bolhuis


Computational Chemistry


van 't Hoff Institute for Molecular Sciences

Project description

T4 lysozyme is an enzyme is used by enterobacteria phage T4 to destroy bacterial cell walls by catalyzing the cleavage of glycosidic bonds. The interaction of T4L with the substrate involves opening and closing of the protein structure, mediated by prominent hinge-bending motion of the two domains. While it has been extensively modelled, the mechanism of this conformational change is not well understood in terms of reaction coordinates [1]. In this project we will use transition path sampling to investigate the mechanism. We will collect and analyse an ensemble of reactive dynamics pathways, that can be scrutinized for important collective variables, to arrive at a prospect reaction coordinate. A proposed four state model will be tested.

[1] Ernst, M., Wolf, S., & Stock, G. (2017). Identification and Validation of Reaction Coordinates Describing Protein Functional Motion: Hierarchical Dynamics of T4 Lysozyme. Journal of Chemical Theory and Computation, 13(10), 5076–5088.

Interested? please apply here

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Incorporating experimental kinetic constraints in molecular dynamics simulations

In this project the student will apply a novel method to incorporate experimental kinetic rate constants in molecular dynamics simulation, using data generated with simple (toy) models, and existing molecular dynamics data on protein folding and conformational changes, together with existing experimental measurements. The project requires some programming skills, knowledge of python. Affinity with theory and mathematical modeling is recommended.

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