On the use of direct-coupling analysis with a reduced alphabet of amino acids combined with super-secondary structure motifs for protein fold prediction

Anton, BernatBesalú, MireiaFornés Crespo, Oriol, 1983-Bonet Martínez, Jaume, 1982-Molina, AlexisMolina Fernández, RubénCuevas, Gemma de lasFernández Fuentes, NarcísOliva Miguel, Baldomero2021-10-262021-10-262021Anton B, Besalú M, Fornes O, Bonet J, Molina A, Molina-Fernandez R, De Las Cuevas G, Fernandez-Fuentes N, Oliva B. On the use of direct-coupling analysis with a reduced alphabet of amino acids combined with super-secondary structure motifs for protein fold prediction. NAR Genom Bioinform. 2021;3(2):lqab027. DOI: 10.1093/nargab/lqab0272631-9268http://hdl.handle.net/10230/48806Direct-coupling analysis (DCA) for studying the coevolution of residues in proteins has been widely used to predict the three-dimensional structure of a protein from its sequence. We present RADI/raDIMod, a variation of the original DCA algorithm that groups chemically equivalent residues combined with super-secondary structure motifs to model protein structures. Interestingly, the simplification produced by grouping amino acids into only two groups (polar and non-polar) is still representative of the physicochemical nature that characterizes the protein structure and it is in line with the role of hydrophobic forces in protein-folding funneling. As a result of a compressed alphabet, the number of sequences required for the multiple sequence alignment is reduced. The number of long-range contacts predicted is limited; therefore, our approach requires the use of neighboring sequence-positions. We use the prediction of secondary structure and motifs of super-secondary structures to predict local contacts. We use RADI and raDIMod, a fragment-based protein structure modelling, achieving near native conformations when the number of super-secondary motifs covers >30-50% of the sequence. Interestingly, although different contacts are predicted with different alphabets, they produce similar structures.application/pdfeng© The Author(s) 2021. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comOn the use of direct-coupling analysis with a reduced alphabet of amino acids combined with super-secondary structure motifs for protein fold predictioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1093/nargab/lqab027info:eu-repo/semantics/openAccess