Protein Structure and Function. Application of Bioinformatics Methods - John Rigden 2014

Comparative Protein Structure Modeling
Applications of Comparative Modeling
Single Protein Modeling

Comparative modeling is frequently an effective way to obtain useful insights into Proteins of interest. For instance, comparative models can be valuable for designing genetic experiments, such as creating mutants to test hypotheses of protein function (Vernal et al. 2002; G Wu et al. 1999), or identifying active sites and binding pockets (Sheng et al. 1996). Such models are useful for studying protein-protein and Protein-Ligand interactions, inhibitor design—such as the discovery, development, and optimization of ligands for a specific binding site (Ring et al. 1993)—substrate Specificity modeling (L. Z. Xu et al. 1996), antigen epitope prediction (Sali et al. 1993), and protein-protein docking simulations (Vakser 1995). Models can also reveal physicochemical properties that cannot be inferred from sequence data alone. For example, insights into protein function can be gained from calculated electrostatic potential surfaces surrounding the protein (Sali et al. 1993), as well as through the general refinement and interpretation of existing experimental data (Fiser et al. 2003). Furthermore, models are highly beneficial for improving structural quality by facilitating molecular replacement in X-ray crystallography (Schwarzenbacher et al. 2008), refining NMR-based models (Barrientos et al. 2001), and validating distant structural relationships (Guenther et al. 1997; G Wu et al. 1999).