Final Activity Report Summary - BIMAMOSI ((Bio)materials molecular simulations)
The BIMAMOSI project addresses the application and development of molecular simulation techniques in (bio)molecular materials design. In the project two approaches were adopted. A detailed atomistic approach to study shape selectivity in zeolites and a course-grained approach to investigate the interactions between proteins in a membrane.
Shape selectivity in zeolite is a simple concept: the transformation of reactants into products depends on how the processed molecules fit the active site of the catalyst. Nature makes abundant use of this concept, in that enzymes usually process only very few molecules, which fit their active sites. Industry has also exploited shape selectivity in zeolite catalysis for almost 50 years, yet our mechanistic understanding remains rather limited. In this project we have developed a fundamental understanding of shape selectivity in zeolite catalysis, and argue that a simple thermodynamic analysis of the molecules adsorbed inside the zeolite pores can explain which products form and guide the identification of zeolite structures that are particularly suitable for desired catalytic applications.
For the understanding of the behaviour of proteins it is important to consider the hydrophobic mismatch, i.e. the difference between the hydrophobic length of the trans membrane protein and the hydrophobic thickness of the lipid bilayer. This misnmatch is an important physical parameter regulating lipid mediated interactions which could play a major role in the organisation and hence the functioning of transmembrane proteins. To study the effect of hydrophobic mismatch on the organisation of membrane proteins we developed a mesoscopic model of a hydrated lipid bilayer with embedded proteins which we studied with dissipative particle dynamics. We observed that short-range hydrophobic interactions between proteins and hydrated lipids lead to long range, indirect, lipid-mediated, protein-protein interactions. To quantify this effect, we first systematically computed the potential of mean force between two embedded proteins as a function of hydrophobic mismatch. Secondly, we studied the lipid-mediated clustering behaviour of proteins as a function of hydrophobic mismatch. For proteins with negative hydrophobic mismatch we observed an unlimited clustering. For proteins without hydrophobic mismatch we observed no lipid-mediated interactions. For proteins with positive mismatch we observed the spontaneous formation of clusters up to a specific size. Our results are in agreement with the relevant experimental results.
Shape selectivity in zeolite is a simple concept: the transformation of reactants into products depends on how the processed molecules fit the active site of the catalyst. Nature makes abundant use of this concept, in that enzymes usually process only very few molecules, which fit their active sites. Industry has also exploited shape selectivity in zeolite catalysis for almost 50 years, yet our mechanistic understanding remains rather limited. In this project we have developed a fundamental understanding of shape selectivity in zeolite catalysis, and argue that a simple thermodynamic analysis of the molecules adsorbed inside the zeolite pores can explain which products form and guide the identification of zeolite structures that are particularly suitable for desired catalytic applications.
For the understanding of the behaviour of proteins it is important to consider the hydrophobic mismatch, i.e. the difference between the hydrophobic length of the trans membrane protein and the hydrophobic thickness of the lipid bilayer. This misnmatch is an important physical parameter regulating lipid mediated interactions which could play a major role in the organisation and hence the functioning of transmembrane proteins. To study the effect of hydrophobic mismatch on the organisation of membrane proteins we developed a mesoscopic model of a hydrated lipid bilayer with embedded proteins which we studied with dissipative particle dynamics. We observed that short-range hydrophobic interactions between proteins and hydrated lipids lead to long range, indirect, lipid-mediated, protein-protein interactions. To quantify this effect, we first systematically computed the potential of mean force between two embedded proteins as a function of hydrophobic mismatch. Secondly, we studied the lipid-mediated clustering behaviour of proteins as a function of hydrophobic mismatch. For proteins with negative hydrophobic mismatch we observed an unlimited clustering. For proteins without hydrophobic mismatch we observed no lipid-mediated interactions. For proteins with positive mismatch we observed the spontaneous formation of clusters up to a specific size. Our results are in agreement with the relevant experimental results.