Annotation of proteins of unknown function: initial enzyme results.

Working with a combination of ProMOL (a plugin for PyMOL that searches a library of enzymatic motifs for local structural homologs), BLAST and Pfam (servers that identify global sequence homologs), and Dali (a server that identifies global structural homologs), we have begun the process of assigning functional annotations to the approximately 3,500 structures in the Protein Data Bank that are currently classified as having "unknown function". Using a limited template library of 388 motifs, over 500 promising in silico matches have been identified by ProMOL, among which 65 exceptionally good matches have been identified. The characteristics of the exceptionally good matches are discussed.

Estimation of protein function using template-based alignment of enzyme active sites.

BACKGROUND: The accumulation of protein structural data occurs more rapidly than it can be characterized by traditional laboratory means. This has motivated widespread efforts to predict enzyme function computationally. The most useful/accurate strategies employed to date are based on the detection of motifs in novel structures that correspond to a specific function. Functional residues are critical components of predictively useful motifs. We have implemented a novel method, to complement current approaches, which detects motifs solely on the basis of distance restraints between catalytic residues. RESULTS: ProMOL is a plugin for the PyMOL molecular graphics environment that can be used to create active site motifs for enzymes. A library of 181 active site motifs has been created with ProMOL, based on definitions published in the Catalytic Site Atlas (CSA). Searches with ProMOL produce better than 50% useful Enzyme Commission (EC) class suggestions for level 1 searches in EC classes 1, 4 and 5, and produce some useful results for other classes. 261 additional motifs automatically translated from Jonathan Barker's JESS motif set [Bioinformatics 19:1644-1649, 2003] and a set of NMR motifs is under development. Alignments are evaluated by visual superposition, Levenshtein distance and root-mean-square deviation (RMSD) and are reasonably consistent with related search methods. CONCLUSION: The ProMOL plugin for PyMOL provides ready access to template-based local alignments. Recent improvements to ProMOL, including the expanded motif library, RMSD calculations and output selection formatting, have greatly increased the program's usability and speed, and have improved the way that the results are presented.

Maternal and contextual influences and the effect of temperament development during infancy on parenting in toddlerhood.

In the current study, latent growth modeling (LGM) was used to: (1) identify the developmental trajectories of infant negative emotions (NE) and regulatory capacity (RC) from 4 to 12 months of age, (2) examine maternal and family factors that may affect NE and RC trajectories, (3) examine transactional associations between developing NE and RC, and (4) examine the effect of infant temperament trajectories on negative parenting when toddlers reached 18 months of age. Mothers from 156 families completed a measure of infant temperament when infants were 4, 6, 8, 10, and 12 months of age and completed maternal relationship stress, depression, and family demographics measures when infants were 4 months of age. Information regarding negative parenting was collected when toddlers reached 18 months of age. LGM results suggest that maternal relationship stress and depression influence infant NE development, that high NE early in infancy may compromise the development of infant regulation, and that steeper decreases of infant RC contribute the greatest amount of variance to negative parenting in toddlerhood. The implications for models of early emotion regulation and incorporating changes in temperament over time into developmentally sensitive models (e.g., emerging parenting practices and developmental psychopathology) are discussed.