DESIGN OF MOLECULAR INTEGRATED ELEMENTS BASED ON THE FLEXIBLE HIGHER ORDER STRUCTURE

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With the aim to establish the designing and constructing principles of integrated molecular system, we studied the structure and working design of biological molecular systems. The model system of our work was animal fatty acid synthetase and alpha-2-macroglobuin, both are multi-functional giant proteins with integrated functional elements. In the case of fatty acid synthetase, seven-enzymes of different partial reactions are integrated into a single functional unit with a definite purpose. When the seven enzymes integrated into two active centers work in a limited space of 20nmxl5nmx7nm, we found that there is a concerted flip-flop type movement of two active centers. Such a movement is probably hydrodynamically coupled with the solvent viscosity and fluctuation as the experimental results on the activity-viscosity relationship clearly indicated. The viscosity dependent movement of the domains and subunits of integrated proteins in large scale will easily be coupled with the chemical rate determining step of the entire reaction. The hydrodynamic coupling between the moving parts of proteins and viscogen molecules added to the aqueous solution of protein was found to be acutely dependent on the size of viscogen. This finding will be exploited in future to estimate the size of the moving elements on the part of the proteins. Similar hydrodynamic coupling of protein movement with solvent is also indicated in the large scale subunit rearrangement of alpha-2- macroglobulin. In this study we made it clear that the hydrodynamic coupling between the elements of integrated system with the solvent is a very important factor to be considered in the design of integrated system on the molecular level.