VADAR (Volume Area Dihedral Angle Reporter) is a comprehensive web server for quantitative protein structure evaluation. It accepts Protein Data Bank (PDB) formatted files or PDB accession numbers as input and calculates, identifies, graphs, reports and/or evaluates a large number (>30) of key structural parameters both for individual residues and for the entire protein. These include excluded volume, accessible surface area, backbone and side chain dihedral angles, secondary structure, hydrogen bonding partners, hydrogen bond energies, steric quality, solvation free energy as well as local and overall fold quality. These derived parameters can be used to rapidly identify both general and residue-specific problems within newly determined protein structures. The VADAR web server is freely accessible at http://redpoll.pharmacy.ualberta.ca/vadar.

A computer program has been developed to accurately and automatically predict the 1H and 13C chemical shifts of unassigned proteins on the basis of sequence homology. The program (called SHIFTY) uses standard sequence alignment techniques to compare the sequence of an unassigned protein against the BioMagResBank--a public database containing sequences and NMR chemical shifts of nearly 200 assigned proteins [Seavey et al. (1991) J Biomol. NMR, 1, 217-236]. From this initial sequence alignment, the program uses a simple set of rules to directly assign or transfer a complete set of 1H or 13C chemical shifts (from the previously assigned homologues) to the unassigned protein. This 'homologous assignment' protocol takes advantage of the simple fact that homologous proteins tend to share both structural similarity and chemical shift similarity. SHIFTY has been extensively tested on more than 25 medium-sized proteins. Under favorable circumstances, this program can predict the 1H or 13C chemical shifts of proteins with an accuracy far exceeding any other method published to date. With the exponential growth in the number of assigned proteins appearing in the literature (now at a rate of more than 150 per year), we believe that SHIFTY may have widespread utility in assigning individual members in families of related proteins, an endeavor that accounts for a growing portion of the protein NMR work being done today.

The relationship between the structure of a free ligand in solution and the structure of its bound form in a complex is of great importance to the understanding of the energetics and mechanism of molecular recognition and complex formation. In this study, we use a structure-based thermodynamic approach to study the dissociation of the complex between the toxin microcystin-LR (MLR) and the catalytic domain of protein phosphatase-1 (PP-1c) for which the crystal structure of the complex is known. We have calculated the thermodynamic parameters (enthalpy, entropy, heat capacity, and free energy) for the dissociation of the complex from its X-ray structure and found the calculated dissociation constant (4.0 x 10(-11)) to be in excellent agreement with the reported inhibitory constant (3.9 x 10(-11)). We have also calculated the thermodynamic parameters for the dissociation of 47 PP-1c:MLR complexes generated by docking an ensemble of NMR solution structures of MLR onto the crystal structure of PP-1c. In general, we observe that the lower the root-mean-square deviation (RMSD) of the docked complex (compared to the X-ray complex) the closer its free energy of dissociation (deltaGd(o)) is to that calculated from the X-ray complex. On the other hand, we note a significant scatter between the deltaGd(o) and the RMSD of the docked complexes. We have identified a group of seven docked complexes with deltaGd(o) values very close to the one calculated from the X-ray complex but with significantly dissimilar structures. The analysis of the corresponding enthalpy and entropy of dissociation shows a compensation effect suggesting that MLR molecules with significant structural variability can bind PP-1c and that substantial conformational flexibility in the PP-1c:MLR complex may exist in solution.

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Exercise interventions with or without educational interventions that can be applied in the workplace have the potential to prevent LBP.