Hierarchical Structure of Protein Sequence

Abstract

Most non-communicable diseases are associated with dysfunction of proteins or protein complexes. The relationship between sequence and structure has been analyzed for a long time, and the analysis of the sequences organization in domains and motifs remains an actual research area. Here, we propose a mathematical method for revealing the hierarchical organization of protein sequences. The method is based on the pentapeptide as a unit of protein sequences. Employing the frequency of occurrence of pentapeptides in sequences of natural proteins and a special mathematical approach, this method revealed a hierarchical structure in the protein sequence. The method was applied to 24,647 non-homologous protein sequences with sizes ranging from 50 to 400 residues from the NRDB90 database. Statistical analysis of the branching points of the graphs revealed 11 characteristic values of y (the width of the inscribed function), showing the relationship of these multiple fragments of the sequences. Several examples illustrate how fragments of the protein spatial structure correspond to the elements of the hierarchical structure of the protein sequence. This methodology provides a promising basis for a mathematically-based classification of the elements of the spatial organization of proteins. Elements of the hierarchical structure of different levels of the hierarchy can be used to solve biotechnological and medical problems.

Relación Estructura–función De Las Proteínas. Uso De La Técnica De Electroforesis en El Estudio De Su Expresión

“…Tales características estructurales resultan de propiedades comunes a todas las cadenas peptídicas (Ealy, 2022), que se forman mediante los enlaces de hidrógeno que estabilizan el esqueleto polipeptídico (Sanvitore & Farci, 2022). Nekrasov et al (2021), analizaron la estructura de las proteínas globulares utilizando diagramas de empaquetamiento, demostrando cómo la disposición de segmentos de estructura secundaria a lo largo de la secuencia se relaciona con propiedades tridimensionales, como las hojas paralelas y antiparalelas.…”

Biophysical Reviews’ “Meet the Councilor”—a profile of Anastasia A. Anashkina

“…A total of 11 levels of protein organization with elements ranging from 7 to 56 amino acid residues were found in the protein sequence set. The organization levels were assumed to correspond to super-secondary structure elements of different topologies (Mikhalskii et al 2020;Nekrasov et al 2020Nekrasov et al , 2021.This method uses the pentapeptide as a unit of protein sequence and has been successfully used in the development of recombinant proteins, the study of the principles of enzyme functioning, and the finding of the minimum functional site in proteins. We analyzed 44,860 structures of peptides by the molecular dynamics method and found that 1,225 pentapeptides over 80% of the simulation time were in a stable conformation.…”

Recent Trends in Cancer Genomics and Bioinformatics Tools Development

“…Overall, the "Medical Genetics, Genomics and Bioinformatics" series collected 28 articles and reviews. This 2021 Special Issue is focused on the analysis of cancer progression [12], genetics mechanisms of cancers [13,14], and bioinformatics theory development [15].…”

“…Alexei Nekrasov et al [15] presented theoretical work on the analysis of hierarchical organization of protein sequences. The authors developed a modeling method based on the pentapeptide as a unit of protein sequences.…”