From Protein Structure to Function with Bioinformatics.pdf

66 A. FiserFig. 3.1 Comparing accuracy (y-axis) of models built for the same set of 765 protein targetsequences using either one template (best E-value hit only; blue bars), or multiple templates(green bars). The percentage of sequence identity (x-axis) is calculated between the hit with thehighest E-value and the query sequence. Error bars indicate standard errors of the mean3.2.3.1 Taking Advantage of Structural Information in AlignmentsAlignments in comparative modelling represent a unique class, because on one sideof the alignment there is always a 3D structure, the template. Therefore alignmentscan be improved by including structural information from the template. For example,gaps should be avoided in secondary structure elements, in buried regions, orbetween two residues that are far in space. Some alignment methods take such criteriainto account (Blake and Cohen 2001; Jennings et al. 2001; Shi et al. 2001).When multiple template structures are available, a good strategy is to superposethem with each other first, to obtain a multiple structure-based alignment highlightingstructurally conserved residues (Al Lazikani et al. 2001; Petrey et al. 2003; Reddyet al. 2001). In the next step, the target sequence is aligned with this multiple structurebasedalignment. The benefits of using of multiple structures and multiple sequencesderive from the evolutionary and structural information about the templates as wellas evolutionary information about the target sequence, and often produces a betteralignment for modelling than the pairwise sequence alignment methods (Jaroszewskiet al. 2000; Sauder et al. 2000).Multiple Mapping Method (MMM) directly relies on information from the 3Dstructure (Rai and Fiser 2006; Rai et al. 2006). MMM minimizes alignment errors byselecting and optimally splicing differently aligned fragments from a set of alternative