Using our KINARI software, we demonstrated that additional functional and rigidity information can be gained by analyzing a protein's biological assembly and/or crystal structure. The rigidity analysis of a single asymmetric unit may not accurately reflect the protein's behavior in the tightly packed crystal environment. The surprising result is that the presence or lack of a very few, but critical, hydrogen bonds, can drastically affect the rigid cluster decomposition of the biological assembly. Upon careful investigation, we tracked the cause to a placement decision by the Reduce software concerning the hydrogen atoms, thus affecting the distribution of certain hydrogen bonds. In contrast, a derivative of Ribonuclease A (PDB file 9RSA), has no functional activity, and the protein in both the asymmetric and crystalline forms, is very rigid.įor the vaccinia virus D13 scaffolding protein (PDB file 3SAQ), which has two biological assemblies, we observed a striking asymmetry in the rigidity cluster decomposition of one of them, which seems implausible, given its symmetry. This type of information, identified here for the first time, depends critically on the ability to create crystals and biological assemblies, and would not have been observed only from the asymmetric unit.įor the Ribonuclease A protein (PDB file 5RSA), which is functionally active in the crystallized form, we found that the individual protein and its crystal form retain the flexibility parameters between the two states. We also identified two interesting cases where rigidity analysis may be correlated with the functional behavior of the protein. (b) In other cases, the rigidity properties of the asymmetric units are retained, because the rigid bodies did not combine. Some of them create substantially larger rigid cluster in the crystal/biological assembly form, while in other cases, the aggregation has a smaller effect just at the interface between the units. (a) Some crystals and/or biological assemblies will aggregate into rigid bodies that span multiple unit cells/asymmetric units. We have analyzed a dataset of approximately 300 proteins, from which we generated 982 crystals (some of which are biological assemblies). Similarly, the rigidity of small crystals may be affected by the interactions between atoms belonging to different unit cells. Indeed, the rigidity of biological assemblies is sometimes dependent on the count and placement of hydrogen bonds and other interactions among the individual subchains of the biological unit. We found that when only isolated subchains are considered, structural and functional information may be missed. We provide two types of results: on biological assemblies and on crystals. Computational experiments were performed using new protein rigidity analysis tools available in the new release of our KINARI-Web server. The analysis relies on an effcient graph-based algorithm. We use experimental X-ray crystallography data from the Protein Data Bank (PDB). The goal is to determine if, and how, the interactions among neighboring cells and subchains affect the flexibility of a molecule in its crystallized state. We initiate in silico rigidity-theoretical studies of biological assemblies and small crystals for protein structures.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |