Availability of short amino acid sequences in proteins

Abstract

Much attention is being paid to protein databases as an important information source for proteome research. Although used extensively for similarity searches, protein databases themselves have not fully been characterized. In a systematic attempt to reveal protein-database characters that could contribute to revealing how protein chains are constructed, frequency distributions of all possible combinatorial sets of three, four, and five amino acids ("triplets," "quartets," and "pentats"; collectively called constituent sequences) have been examined in the nonredundant (nr) protein database, demonstrating the existence of nonrandom bias in their "availability" at the population level. Nonexistent short sequences of pentats were found that showed low availability in biological proteins against their expected probabilities of occurrence. Among them, six representative ones were successfully synthesized as peptides with reasonably high yields in a conventional Fmoc method, excluding the possibility that a putative physicochemical energy barrier in forming them could be a direct cause for the low availability. They were also expressed as soluble fusion proteins in a conventional Escherichia coli BL21Star(DE3) system with reasonably high yield, again excluding a possible difficulty in their biological synthesis. Together, these results suggest that information on threedimensional structures and functions of proteins exists in the context of connections of short constituent sequences, and that proteins are composed of evolutionarily selected constituent sequences, which are reflected in their availability differences in the database. These results may have biological implications for protein structural studies.

Forbidden penta‐peptides

“…1 All penta-peptides that were reported as missing in the work of Otaki and colleagues do appear in our database, which is more up-to-date (and more than four times larger than the data set Otaki and colleagues used) (Otaki et al 2005). 2 Hampikian and Andersen mainly describe a method for fast calculation of k-mers that do not appear in a set of proteins.…”

“…Many bioinformatic investigations have explored the sequences of amino acids in proteins (see, for example, Gavel and Heijne 1992;Echols et al 2002;Qi et al 2004;White and Heijne 2004;Otaki et al 2005;White and Heijne 2005;Ulitsky et al 2006;Hampikian and Andersen 2007), or have attempted to model proteins by various probability models (Krogh et al 1994;Abe and Mamitsuka 1997;Durbin et al 1998;Bystroff et al 2000;Eddy 2004). Otaki and colleagues 1 (Otaki et al 2005) have examined the space of ''missing'' AA sequences and have discovered the missing penta-peptides.…”

“…Otaki and colleagues 1 (Otaki et al 2005) have examined the space of ''missing'' AA sequences and have discovered the missing penta-peptides. Their analysis, however, did not take into account the non-coding parts of the genome.…”

Genomic DNA k-mer Spectra: Models and Modalities

“…The most basic empirical question that has been investigated is that of missing DNA k-mers. Earlier works have studied non-existent short amino acid k-mers [3,4], and have attributed them mainly to chemical constraints (such as hydrophobic and hydrophilic amino acids). DNA does not have the complex three-dimensional structure and chemical constraints of proteins, although the nucleotide composition has been reported by el antri et al [5] to weakly affect the structure of double-stranded DNA.…”

Amino acid sequence repertoire of the bacterial proteome and the occurrence of untranslatable sequences

“…Short-sequence use has been analyzed previously (17)(18)(19)(20), and different reasons for a lack of some sequences have been suggested. Our bioinformatics results identify triplet and quadruplet sequences that slow translation and lead to stalling almost immediately upon entry into the exit tunnel.…”