Finkelstein, A. V. | bioRxiv Science

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↗