Tertiary protein structure viewing and prediction.pptVIP

Tertiary protein structure viewing and prediction July 3, 2007 Learning objectives- Learn how to manipulate protein structures with Deep View software. Learn the steps to protein structure modeling with Deep View. Workshop-Manipulation of the lysozyme and hemoglobin. Protein structure viewers RasMol Deep View Cn3D WebLabViewer Chimera Steps to tertiary structure prediction Comparative protein modeling Extrapolates a new structure based on solved structures that are related by sequence. Step 1: Identification of modeling templates One chooses a cutoff value from FastA or BLAST search ( E10-5) and perform BLAST search of Protein Data Bank. Up to ten structure templates can be used but the one with the highest sequence similarity to the target sequence (lowest E-value) is designated as the reference template. Its structure is given the most weight. Ca atoms of the templates are selected for superimposition. This generates a structurally corrected multiple sequence alignment Step 2: Alignment Up to 5 template structures are superimposed. Incompatible templates are removed. Pairwise alignment is created between target and main template structures. Step 3: Building the model Framework construction Average the position of each atom in target sequence, based on the corresponding atoms in template (start with C ? atoms) Step 3: Building the model Completing the backbone-a library of PDB entries is consulted to add carbonyl groups and amino groups. The 3-D coordinates come from a separate library of pentapeptide backbone fragments. These backbone fragments are fitted onto the target C alpha carbons. The central tri-peptide atoms are averaged from each backbone atom (N,C,C(O)). Side chains are added from a table of most probable rotamers given a certain backbone conformation. Step 4: Energy Minimization Model refinement-minimization of energy (GROMOS96 force field) * * Steps for SWISS-Model Identification of modeling templates. Alignment between target and template