Mechanism of processivity in hyaluronate lyase
Using atomistic molecular dynamics simulation, the aim is to understand the mechanism of processive hyaluronan degradation by the enzyme hyaluronate lyase. Particularly the interplay between protein dynamics and sugar translocation in the protein's binding cleft is investigated.
Prediction of macromolecular flexibility from geometrical constraints
Protein dynamics is often a prerequisite for function. Molecular dynamics simulations are routinely used to predict dynamic modes essential to function. However, such techniques often suffer from severe sampling limitations. In this project we use the CONCOORD approach to overcome these limitations by an exhaustive sampling of the configurational space within predefined boundaries that are estimated from interactions in the native conformation.
An efficient sampling algorithm for the simulation of biomolecular systems
One of the main reasons for the sampling limitations of conventional molecular dynamics simulations is the ruggedness of the potential energy landscape, resulting in a high probablity of being trapped in a small number of local minima. Combining the ideas of essential dynamics and replica exchange molecular dynamics, we investigate the possibilities of deriving an efficient sampling protocol to be used in simulations of biomolecular systems.
The selectivity mechanism of aquaporins
Aquaporins are universal water channels in biological membranes. Molecular dynamics simulations have contributed significantly to our current understanding of the mechanism of water permeation and selectivity against protons. In this project we aim at understanding the molecular determinants underlying the mechanism of selectivity: why are some water channels solely permable to water, whereas others may also permeate other small solutes, gases, or even ions?
Design of model water channels
Using gramicidin as a starting model, the goal of this project is to design model water channels with modified permeation characteristics. In close collaboration with experiment, both the efficiency and selectivity of these model water channels are systematically modulated, thereby providing insight in the factors determining permeation characteristics.