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Biomedical subjects

N N Alexandrov

Publications and source records attributed to N N Alexandrov.

5 recordsLinked to original sources

Common spatial arrangements of backbone fragments in homologous and non-homologous proteins.

We have developed a new method of detecting common spatial arrangements of backbone fragments in proteins. This method allows corresponding fragments to occur in a different order in respective amino acid sequences. We applied this method to detect structural similarities between an acid protease, endothiapepsin, and all other proteins in the protein data bank. Significant similarities were found not only with other acid proteases but also with virus proteases and with proteins having different functions. The possible biological meaning of these similarities is discussed.

Aspartic Acid Endopeptidases

Local multiple alignment by consensus matrix.

A new algorithm for aligning several sequences based on the calculation of a consensus matrix and the comparison of all the sequences using this consensus matrix is described. This consensus matrix contains the preference scores of each nucleotide/amino acid and gaps in every position of the alignment. Two modifications of the algorithm corresponding to the evolutionary and functional meanings of the alignment were developed. The first one solves the best-fitting problem without any penalty for end gaps and with an internal gap penalty function independent on the gap length. This algorithm should be used when comparing evolutionary-related proteins for identifying the most conservative residues. The other modification of the algorithm finds the most similar segments in the given sequences. It can be used for finding those parts of the sequences that are responsible for the same biological function. In this case the gap penalty function was chosen to be proportional to the gap length. The result of aligning amino acid sequences of neutral proteases and a compilation of 65 allosteric effectors and substrates of PEP carboxylase are presented.

Algorithms

Application of a new method of pattern recognition in DNA sequence analysis: a study of E. coli promoters.

An algorithm from the pattern recognition theory 'generalized portrait' was used to find a distinguishing vector (scoring matrix) for E. coli promoters. We have attempted to solve three closely linked problems: (i) the selection of significant features of the signal; (ii) subsequent multiple alignment and (iii) calculation of the vector coordinates. Promoters with known strength have been successfully ranked in the correct order using this vector. We demonstrate the use of this method in predicting the location of promoters. A revised consensus promoter sequence is also presented.

Algorithms

Statistical method for rapid homology search.

A new method for homology search of DNA sequences is suggested. This method may be used to find extensive and not strong homologies with point mutations and deletions. The running program time for comparing sequences is less then the dynamic program algorithms at least at two orders of magnitude. It makes possible to use the method for homology searching throughover the nucleotide bank by personal computers.

Algorithms