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Thrombin – Na-dependent serine protease that plays a key role in blood coagulation cascade. Large amount of structural data was accumulated during long story of studies. Thrombin one of the most widespread proteins in PDB – there are 322 entries for human thrombin only. They consist of wild type and mutant pro- teins with varying length because of missing parts of flexible loops. However many of them are known to be almost identical in terms of Ca RMSD. Considering that, the aim of the work is to find small number of reference structures that are able to cover all the conforma- tions available in PDB. 548 SW06 General Aspects of Biochemistry Using similarity metric based on all-atom RMSD and Affinity propagation clustering algorithm, with a probability for a struc- ture to become reference depending on resolution, we subdivided all the 364 individual thrombin molecules from PDB into 14 groups and extracted reference structures. Nine groups are large, very uniform and represent thrombin in the active state. The 5 others are small (not >5 structures), dis- tinctly differ primarily in the area of sodium binding site and active site cleft environment and represent conformational ensem- ble of thrombin in the inactive state. Transitions between states corresponding to extracted refer- ences were observed by molecular dynamics simulations. Obtained results can be used in the development of next-gen- eration anticoagulants and in crystallographic studies.