Generating coordinates for unknown structure in Homology

Generating coordinates for unknown structure: When we want to generate the coordinates of unknown structure we need to model both main chain atoms and sub chain atoms in both SCRs and VRs.In case of SCRs it is a straight process to generate the coordinates of main chain atoms of unknown structures with the reference of known structures. But the side chain coordinates are copied if the residues in the unknown structure are identical or very similar to the known ones. For the other one chain coordinates we can apply a side chain rotamer library in a systematic approach to find out all possible side chain confirmations. It may be desirable to weight the contribution of each homologue in each SCR based on the extent of similarity with the unfamiliar. In the event that several coordinates in the unknown are undefined in the SCRs, regularization can be employed to build and relax both main chain and side chain atoms in such regions. Note that this procedure must be used only if the area of undefined atoms is one or two residues in length. In case of VRs we have to go with different kinds of applications to assign coordinates to unknown. We have already seen that these loops correspond most often to the loops on the surface of the protein. If we have a loop in the known structure which can become a good model for the unknown, then we can copy the main coordinates of known structure. We can also copy the side chain residues that are of similar length. Here Rotamer libraries are used to define other chain coordinates. When we cannot find a good model in known structures the fragment databases can be searched for loops in other proteins which can provide a suitable model for unknown. We have to chose a residue range to include the undefined loop as well as a few residues (e.g., three) on either side of the loop for which coordinates have been defined. Fragment examination is done for their ability to fit in the undefined region without making bad contacts with other atoms and to overlap well with the residues on either side of the loop. The loop might then be subjected to conformational searching to identify low energy conformers when desired. Coordinates for side chain atoms in such loop regions might be copied if residues are similar, although it is likely that considerable application of side chain rotamer libraries will be required to define coordinates in these regions.

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