Practical Guide to Homology Modeling: Difference between revisions
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The 18 residues marked X were not included in the identity calculation. In contrast, when the same sequence search is performed at [http://www.ebi.ac.uk/pdbe PDB-Europe], 100% sequence identity is reported. However, other aspects of the report at PDB-Europe are less satisfactory (e.g. the length of the alignment is not stated; the sequences are not numbered) and hence we recommend using pdb.org despite its misleading sequence identity percentages. But you may certainly want to run the sequence search at [http://www.ebi.ac.uk/pdbe PDB-Europe] to compare the reported identity percentages. | The 18 residues marked X were not included in the identity calculation. In contrast, when the same sequence search is performed at [http://www.ebi.ac.uk/pdbe PDB-Europe], 100% sequence identity is reported. However, other aspects of the report at PDB-Europe are less satisfactory (e.g. the length of the alignment is not stated; the sequences are not numbered) and hence we recommend using pdb.org despite its misleading sequence identity percentages. But you may certainly want to run the sequence search at [http://www.ebi.ac.uk/pdbe PDB-Europe] to compare the reported identity percentages. | ||
== Are parts (or all) of the query protein intrinsically disordered? == | |||
Although fold is required for the function of most proteins, some proteins are [[Intrinsic Disorder|intrinsically disordered]] (natively unstructured) and do not fold, at least by themselves. Often, intrinsically disordered protein transitions to an ordered state when it binds to a folded partner protein. However some proteins remain disordered while performing their functions. | |||
By some estimates, 10% of proteins are intrinsically disordered for their full lengths, and about 40% of eukaryotic proteins have at least one loop 50 residues or longer that is intrinsically disordered. These disordered loops are typically missing from X-ray crystallographic structures because the disorder blurs that portion of the electron density map. | |||
Examples: | |||
*Folded: Pyruvate kinase (length 531; e.g. [http://mobidb.bio.unipd.it/entries/P11979 P11979, KPYM_FELCA]) has no disordered regions. The crystal structure (1pkm) lacks only 11 residues at the C terminus. | |||
*Partially folded: The tumor suppressor protein p53 (length 393; e.g. P04637, P53_HUMAN) is intrinsically disordered at both the N and C termini. There are many crystallographic structures for the folded mid-region (~200 residues), which lack coordinates for 90-some residues at the N terminus, and 90-some at the C terminus. Some solution NMR structures of the N terminus illustrate the disorder (e.g. 2ly4). | |||
*Unfolded: Caldesmon from chicken gizzard (length 771; P12957, CALD1_CHICK) has no crystal structures, and is predicted to be disordered for essentially its full length. | |||
Attempts to determine structure for intrinsically disordered protein will be futile. Therefore, before considering homology modeling or crystallization experiments, it is important to predict whether portions of the query protein are likely to be intrinsically disordered. | |||
== References == | == References == | ||
<references/> | <references/> | ||
