| Abstract: | Theoretical conformational investigation of the thrombin-fibrinogen recognition complex was fulfilled. At first preliminary study was carried out using space-filling molecular models. At the next stage computer simulation was conducted. For this purpose a package of programs for the theoretical conformational analysis of two interacting molecules has been developed in the framework of atom-atom potentials. The package contains an original algorithm for constructing initial approximation based on assumption that the structure of the complex is determined mainly by the ligand-ligand attraction and Van-der-Vaals repulsion. Complex structure with considerable binding energy was obtained. Molecules of that structure are bound mainly by four oppositely charged pairs of side chain groups. The beta -loop of thrombin in the complex is shown to undergo essential structural transformations. A hypothesis is suggested that this transformation may influence active sites allosterically. Some ways and mechanisms of this influence are discussed as well as an approach to its calculation. |
