Associating protein sequence positions with the modulation of quantitative phenotypes

Arch Biochem Biophys. 2024 Apr 5:109979. doi: 10.1016/j.abb.2024.109979. Online ahead of print.ABSTRACTAlthough protein sequences encode the information for folding and function, understanding their link is not an easy task. Unluckily, the prediction of how specific amino acids contribute to these features is still considerably impaired. Here, we developed a simple algorithm that finds positions in a protein sequence with potential to modulate the studied quantitative phenotypes. From a few hundred protein sequences, we perform multiple sequence alignments, obtain the per-position pairwise differences for both the sequence and the observed phenotypes, and calculate the correlation between these last two quantities. We tested our methodology with four cases: archaeal Adenylate Kinases and the organisms optimal growth temperatures, microbial rhodopsins and their maximal absorption wavelengths, mammalian myoglobins and their muscular concentration, and inhibition of HIV protease clinical isolates by two different molecules. We found from 3 to 10 positions tightly associated with those phenotypes, depending on the studied case. We showed that these correlations appear using individual positions but an improvement is achieved when the most correlated positions are jointly analyzed. Noteworthy, we performed phenotype predictions using a simple linear model that links per-position divergences and differences in the observed phenotypes. Predictions are comparable to the state-of-art ...

Source: Archives of Biochemistry and Biophysics - April 7, 2024 Category: Biochemistry Authors: Ayel én S Hernández Berthet Ariel A Aptekmann Jes ús Tejero Ignacio E S ánchez Mart ín E Noguera Ernesto A Roman Source Type: research