Objective
In this project detailed investigation of the structural properties and permeability of several fully hydrated lipid membranes is planned by computer simulation methods (MC and MD). One-component membranes of various saturated and unsaturated phospholipid molecules as well as binary phospholipid/cholesterol mixed membranes are intended to study. The studies are planned to be performed in a systematic way, analysing the effect of the cholesterol molecule and the C=C double bonds independently from each other and from other factors. The effect of the cholesterol molecule and the unsaturated hydrocarbon chains on the structural and dynamical properties of the nearby phospholipid molecules is intended to be analysed. The observed effects can be related to the change of the properties of the entire membrane due to these constituents, allowing a molecular level interpretation of the structure forming role of these molecules in the membrane.
Among the investigated membrane characteristics special attention is devoted to the free volume properties. The distribution of the free volume pockets as well as that of their shape, size and connectivity in a lipid membrane is closely related to the primary biological function of the membrane, e.g. the regulation of the passive crossmembrane transport of various penetrants. The origin of the membrane selectivity is believed to be closely related to the free volume properties, and hence the planned studies can help to clarify the molecular level origin of these processes. Moreover, the planned work provides an opportunity to investigate the role of the cholesterol molecule and the unsaturated hydrocarbon chains in the determination of the membrane permeability. Since the diffusion of small penetrants in biological membranes is found experimentally to be similar with that in soft polymers, the proposed project also aims the investigation of the relation of the free volume properties and permeability of various soft polymers as homogeneous reference systems. Such a comparison of the properties of lipid membranes and soft polymers can help to distinguish between different regions of the inhomogeneous membrane according to their importance in the permeation process.
The exact determination of the free volume distribution of a complex system, consisting of a large number of atoms of various sizes, such as the lipid membrane models, is a rather complicated and computationally demanding task. The proposed project intends to develop and implement a new methodology for it. The planned approach for quantitative analysis of the free volume is based on the determination and analysis of the Voronoi-Delaunay tessellation of the system. A key problem of this analysis is to find an efficient algorithm for the calculation of the Voronoi network of a complex molecular system. A computational cost of the planned algorithm should increase linearly with the number of atoms. A set of algorithms and programs for calculation of different characteristics of free volume should also be developed.
Among the four participating groups the Novosibirsk team will be responsible for developing the computer code for the Voronoi-Delaunay analyses and for performing these calculations. The Italian team is going to perform the simulations of the soft polymer systems and analyse the obtained results. The effect of cholesterol on the membrane properties will be investigated by the Hungarian group, whereas that of the unsaturated chains by the Karelian team.
Topic(s)
Call for proposal
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1117 Budapest
Hungary