A MONTE-CARLO SIMULATION STUDY OF PROTEIN-INDUCED HEAT-CAPACITY CHANGES AND LIPID-INDUCED PROTEIN CLUSTERING

Monte Carlo simulations were used to describe the interaction of perip heral and integral proteins with lipids in terms of heat capacity prof iles and protein distribution. The simulations were based on a two-sta te model for the lipid, representing the lipid state as being either g el or fluid. The interaction between neighboring lipids has been taken into account through an unlike nearest neighbor free energy term Delt a omega, which is a measure of the cooperativity of the lipid transiti on. Lipid/protein interaction was considered using the experimental ob servation that the transition midpoints of lipid membranes are shifted upon protein binding, a thermodynamic consequence of different bindin g constants of protein with fluid or gel lipids. The difference of the binding free energies was used as an additional parameter to describe lipid-protein interaction. The heat capacity profiles of lipid/protei n complexes could be well described for both peripheral and integral p roteins. Binding of proteins results in a shift and an asymmetric broa dening of the melting profile. The model results in a coexistence of g el and fluid lipid domains in the proximity of the thermotropic transi tion. As a consequence, bound peripheral proteins aggregate in the tem perature range of the lipid transition. Integral proteins induce calor imetric melting curves that are qualitatively different from that of p eripheral proteins and aggregate in either gel or liquid crystalline l ipid phase. The results presented here are in good agreement with calo rimetric experiments on lipid-protein complexes and have implementatio ns for the functional control of proteins.