Biology subjects

Finkelstein, A. V.

Publications and source records attributed to Finkelstein, A. V..

3 recordsLinked to original sources

bioRxiv2023

Where to stop psi-BLAST iterations so that the found sequences remain related to the query sequence?

The BLAST program [Altschul et al., 1990, J. Mol. Biol., 215:403-410] stands as a widely used tool for the search of the most similar sequences, while the iterative {Psi}-BLAST program [Altschul et al., 1997, Nucl. Acids Res., 25:3389-3402] offers a high sensitivity for detecting remote homologs of the query sequence through an iterative usage of the BLAST search. However, the number of iterations that have to be used by the {Psi}-BLAST is rather poorly justified in the literature. Our study shows that, as the number of iterations increases, {Psi}-BLAST rapidly loses the ability to be guided by the query sequence in the search for homologs. When working with the non-redundant (nr) sequence database of 2021, {Psi}-BLAST, already after the second iteration, retains the query sequence at the top of the list of the found homologs to this sequence in only 18% of cases. Moreover, a query sequence is still listed among homologs found by {Psi}-BLAST after the recommended 10 iterations [Altschul et al., 1997, Nucl. Acids Res., 25:3389-3402] in only 42% of cases. Using a considerably smaller nr database-2011 as a reference, we reveal that these effects intensify over time. Our findings underscore the necessity for circumspection when interpreting {Psi}-BLAST outcomes; the degree of vigilance must increase with the database size. A vigilant monitoring of the position of the query sequence in the array of detected homologs is needed. We recommend using the disappearance of the query sequence from the list of homologs produced by {Psi}-BLAST as a criterion to conclude the {Psi}-BLAST iterations.

bioinformatics↗

bioRxiv2022

Does AlphaFold predict the spatial structure of a protein from physics or recognize it (its main parts and their association) using databases?

The great success of the AlphaFold programs poses the following questions: (i) What is the main reason for this success? (ii) What exactly do AlphaFolds do: prediction of the 3D protein structure based on its amino acid sequence and knowledge of the protein physics or recognition of this 3D structure, based on the similarity between some parts of its amino acid sequence and parts of sequences with already known 3D structures? The answers given in this paper are: The main reason for the tremendous success of the AlphaFold is (i) the usage of huge protein databases, which already cover all or almost all of the protein superfamilies existing in nature; (ii) using these databases and the resulting multiple sequence alignments and coevolutionary information (like correlations in pairs and especially in triplets of amino acid residues in the contacting chain regions), AlphaFold recognizes a 3D structure of the examined amino acid sequence by a similarity of this sequence (or its parts) to related sequences with already known 3D structures. Concluding, I have to emphasize that this paper does not diminish the merit and utility of AlphaFold; it only explains the basis of its success.

bioinformatics↗

bioRxiv2021

A novel view on the mechanism of biological activity of antifreeze proteins

The adaptation of organisms to sub-zero temperatures is an intriguing problem in biology and biotechnology. The ice-binding antifreeze proteins are known to be responsible for the adaptation, but the mechanism of their action is still far from being clear. Here we show that: (i) in contrast to common belief, ice-binding proteins do not reduce the water freezing temperature and even raise (1) the ice melting point; (ii) at sub-zero temperatures (to {approx} -30{degrees}C), ice can be formed only on ice-binding surfaces, but, for kinetic reasons, not in bulk water; (iii) living cells have some large surfaces, which can bind the antifreeze proteins. These facts allow suggesting that the task of antifreeze proteins is not to bind to the ice crystals already formed in the cell and stop their growth or rearrangement, but to bind to those cell surfaces where the ice nuclei can form, and thus to prevent ice formation completely.

biophysics↗