 Dear students, now we are going to review the chapter of homology modeling or structure modeling. You know that the protein structure is generally divided into four strata. The first level of structure formation is the primary structure. The second is the secondary, tertiary and quaternary structures. So given that we have these secondary and tertiary structures as well as quaternary structures, why do we need to go for structural modeling or homology modeling? So the reason for that is that the number of structures that are known through experiments is very few as compared to the number of sequences that we have. So to predict the structures of a lot of proteins, we need homology modeling or structural modeling. We looked at the details of three different structural modeling strategies. The first one was homology modeling. In homology modeling what we did was we performed sequence alignment of proteins and we looked at the homologues of the sequences. So once we obtain the homologues, then we search the protein databases, the structural databases to retrieve their structures. If we could find those structures for the homologues sequences, then we try to see how these structures can be taken up by the query sequence. Several steps existed, specifically seven steps existed in homology modeling, which tuned this process and gave you an optimal structure. In cases where homology modeling did not work, we looked at the fold recognition. So if the overall structure of the protein does not conform to the sequence that we have, then we started looking at specific portions of the structure, that were the folds. So by looking at each fold within a fold database, we try to see which fold fits which portion of your sequence. And once the entire sequence was assigned a specific fold, then we could say the overall structure of the protein. However, there could be a case where you could not even find folds. So in such a case you are left with no option but ab initio modeling. So in ab initio modeling we looked at the atomic level interactions between the protein backbone and we optimize it using molecular dynamic simulations. Why did we have these three types of structural modeling approaches? So if you look at this graph, we had alignment on the horizontal axis and sequence identity on the vertical axis. So if you have a high alignment score and high identity, then we could go for homology modeling. So this is a very important point that you should remember. So this is the area where homology modeling can work very nicely. However, if the identity was low or the alignment was low, then we had two options. One was to go for fold recognition or threading. And the second option was ab initio modeling. So by looking at the alignment length and the identity, we need to determine which approach we are going to take from these two. So we also looked at the protein data bank database and we saw how several structures can be obtained from the PDB. Lastly, we looked at the eye tesser as well as the modeler. Eye tesser was used to thread or perform fold recognition on sequences for which the structures were unknown.