Topic 2 John Markley

Task: choice of targets that meet selection criteria and are likely to yield structures Models from sequences: ORFs, intron/exon boundaries, Pfam, conserved residues, coordinately modified residues, secondary structure, low complexity, disorder, MW, pI, solubility, leader sequences, transmembrane regions, UV absorbance Models from experimental data: structures of similar sequences, functional annotation, biomedical relevance, protein:protein interactions, metabolic pathways, small molecule databases, targetDB, pepcDB Useful models in high-throughput protein structure determinations: 1

Useful models in high-throughput protein structure determinations: 2 Tasks: design of construct and expression system; redesign of targets that fail Models of constructs, primers, vectors, host systems Models of crystallization screens; crystal recognition models Models for evaluating NMR screening results (peak counts, peak widths, shifts indicative of ordered helix and strand) Models assisting in the redesign (mutation / truncation) of targets that fail in the above

Useful models in high-throughput protein structure determinations: 3 Tasks: probabilistic NMR structure determination Models of chemical shift priors based on aa sequence and experiment type Interactive, adaptive modeling of nD NMR data as they are collected Modeling of ambiguous assignments Models for identifying helix, strand, and diverse regions of the peptide chain Models for sharpening of probabilities for structural constraints 3D structural models and their agreement with experimental constraints and bioinformatic priors