Search PubMed⌕ Search

Biomedical subjects

C A Orengo

Publications and source records attributed to C A Orengo.

6 recordsLinked to original sources
PubMed1992

Fast structure alignment for protein databank searching.

A fast method is described for searching and analyzing the protein structure databank. It uses secondary structure followed by residue matching to compare protein structures and is developed from a previous structural alignment method based on dynamic programming. Linear representations of secondary structures are derived and their features compared to identify equivalent elements in two proteins. The secondary structure alignment then constrains the residue alignment, which compares only residues within aligned secondary structures and with similar buried areas and torsional angles. The initial secondary structure alignment improves accuracy and provides a means of filtering out unrelated proteins before the slower residue alignment stage. It is possible to search or sort the protein structure databank very quickly using just secondary structure comparisons. A search through 720 structures with a probe protein of 10 secondary structures required 1.7 CPU hours on a Sun 4/280. Alternatively, combined secondary structure and residue alignments, with a cutoff on the secondary structure score to remove pairs of unrelated proteins from further analysis, took 10.1 CPU hours. The method was applied in searches on different classes of proteins and to cluster a subset of the databank into structurally related groups. Relationships were consistent with known families of protein structure.

Amino Acid Sequence↗
PubMed1990

A rapid method of protein structure alignment.

A reduction in the time required to compare two protein structures has been achieved for a previously developed structure alignment method, by reducing the number of residue pair comparisons which must be performed between the two structures. Subsets of residue pairs are selected by an iterative procedure. Initially, selection is based on similarities in solvent accessible surface areas or torsional angles or a combination of both properties, giving subsets containing approximately 2% of the total number of residue pairs. Using these subsets, a rough comparison of the two structures is generated by the structural alignment program. The information returned from this can be used to identify more accurately topologically equivalent residues in the two proteins, thus enabling a new and much smaller subset (less than 0.2% of the total number of residue pairs) to be selected. The process of iterative refinement of the residue pair subsets is repeated once more, when in 95% of the structure comparisons tested, the correct alignment of the proteins was obtained. Times required to compare the structures using the refined subsets are insignificant compared to the initial comparison, so that considerable increases in speed are possible. The method was tested on two groups of proteins, a set of remotely related alpha/beta nucleotide proteins and the variable and constant domains of the immunoglobulins. Increases in speed ranging from 50-fold to greater than 150-fold were obtained depending on the degree of similarity of the two structures. In some comparisons the alignment was improved due to the reduction in noise obtained by comparing mainly equivalent residues.

Computer Simulation↗
PubMed1989

Protein structure alignment.

A new method of comparing protein structures is described, based on distance plot analysis. It is relatively insensitive to insertions and deletions in sequence and is tolerant of the displacement of equivalent substructures between the two molecules being compared. When presented with the co-ordinate sets of two structures, the method will produce automatically an alignment of their sequences based on structural criteria. The method uses the dynamic programming optimization technique, which is widely used in the comparison of protein sequences and thus unifies the techniques of protein structure and sequence comparison. Typical structure comparison problems were examined and the results of the new method compared to the published results obtained using conventional methods. In most examples, the new method produced a result that was equivalent, and in some cases superior, to those reported in the literature.

Algorithms↗
PubMed1989

A holistic approach to protein structure alignment.

A method of protein structure comparison developed previously is extended to incorporate other aspects of protein structure in addition to the inter-atomic vectors on which it was originally based. Each additional aspect, which induced hydrogen bonding, solvent exposure, torsional angles and sequence, was introduced separately and evaluated for its ability to improve alignment quality. The components were then combined, suitably weighted, to produce a more holistic comparison method. The method was tested on a group of remotely related beta/alpha type proteins that share a common feature in their overall chain fold. The results indicated that while the original inter-atomic vector component was sufficient to give the correct alignment of most pairs of topologically equivalent proteins, the inclusion of hydrogen bonds, torsion angles and a measure of solvent exposure led to improvements in the more difficult comparisons. Consideration of amino acid properties, including hydrophobicity, had no beneficial effect. The failure of the latter component was not unexpected considering the almost total lack of sequence similarity among the proteins considered.

Chemistry, Physical↗
PubMed1987

Interactions between estrogen and EGF in uterine growth and function.

The rat uterus contains specific, high-affinity EGF receptors which possess a tyrosine kinase activity. As demonstrated autoradiographically, these receptors are present in the epithelial, stromal and myometrial cells of the uterus. Estrogen treatment in vivo produces a 2-3-fold increase in EGF receptor levels in the immature rat, the immature mouse and the ovariectomized adult rat; furthermore, EGF receptor levels vary throughout the estrus cycle in concert with levels of occupied nuclear estrogen receptor. This estrogen-induced increase in EGF receptor is preceded by an increase in the level of EGF receptor mRNA as judged by Northern blot analysis. In general, there is a good correlation between estrogen-induced DNA synthesis and EGF receptor levels in the uterus, although in certain situations EGF receptor levels are elevated without a subsequent increase in DNA synthesis. These observations suggest that an increase in tissue EGF receptor levels is important in estrogen-induced uterine growth, but that this increase in receptor levels alone is not sufficient to stimulate DNA synthesis. In addition to its possible role in tissue growth, we have shown very recently that EGF causes contraction of myometrial smooth muscle in a completely in vitro organ bath system. The qualitative nature of this contractile response is distinct from that produced by other classical uterotonic agents. The physiological significance of this uterine response to EGF remains to be elucidated.

Animals↗