Structural and functional restraints on the occurrence of single amino acid variations in human proteins
| Autor: | Tom L. Blundell, Sungsam Gong |
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| Přispěvatelé: | Gong, Sung [0000-0001-5796-4423], Blundell, Tom [0000-0002-2708-8992], Apollo - University of Cambridge Repository |
| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular lcsh:Medicine Computational Biology/Macromolecular Structure Analysis Sequence alignment Plasma protein binding Biology Protein Structure Secondary 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Protein structure Genetic variation Human proteome project Side chain Humans Genetic Predisposition to Disease lcsh:Science Databases Protein Protein secondary structure Genetics and Genomics/Cancer Genetics 030304 developmental biology Genetics chemistry.chemical_classification 0303 health sciences Multidisciplinary Binding Sites Polymorphism Genetic lcsh:R Genetic Variation Proteins Computational Biology/Macromolecular Sequence Analysis Hydrogen Bonding Genetics and Genomics/Bioinformatics Amino acid Protein Structure Tertiary chemistry Amino Acid Substitution Mutation lcsh:Q 030217 neurology & neurosurgery Research Article Protein Binding |
| Zdroj: | PLoS ONE; Vol 5 PLoS ONE PLoS ONE, Vol 5, Iss 2, p e9186 (2010) |
| DOI: | 10.17863/cam.38945 |
| Popis: | Human genetic variation is the incarnation of diverse evolutionary history, which reflects both selectively advantageous and selectively neutral change. In this study, we catalogue structural and functional features of proteins that restrain genetic variation leading to single amino acid substitutions. Our variation dataset is divided into three categories: i) Mendelian disease-related variants, ii) neutral polymorphisms and iii) cancer somatic mutations. We characterize structural environments of the amino acid variants by the following properties: i) side-chain solvent accessibility, ii) main-chain secondary structure, and iii) hydrogen bonds from a side chain to a main chain or other side chains. To address functional restraints, amino acid substitutions in proteins are examined to see whether they are located at functionally important sites involved in protein-protein interactions, protein-ligand interactions or catalytic activity of enzymes. We also measure the likelihood of amino acid substitutions and the degree of residue conservation where variants occur. We show that various types of variants are under different degrees of structural and functional restraints, which affect their occurrence in human proteome. |
| Databáze: | OpenAIRE |
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