Protein Homology Modeling for Effective Drug Design

The effective drug design, especially for combating the multi-drug-resistant bacterial pathogens, requires more and more sophisticated procedures to obtain novel lead-like compounds. New classes of enzymes should be explored, especially those that help bacteria overcome existing treatments. The homology modeling is useful in obtaining the models of new enzymes; however, the active sites of them are sometimes present in closed conformations in the crystal structures, not suitable for drug design purposes. In such difficult cases, the combination of homology modeling, molecular dynamics simulations, and fragment screening can give satisfactory results.