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Protein dynamics analysis reveals that missense mutations in cancer‐related genes appear frequently on hinge‐neighboring residues
Author(s) -
Sayılgan Jan Fehmi,
Haliloğlu Türkan,
Gönen Mehmet
Publication year - 2019
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25673
Subject(s) - missense mutation , gene , genetics , biology , kras , mutation , cancer research
Missense mutations have various effects on protein structures, also leading to distorted protein dynamics that plausibly affects the function. We hypothesized that missense mutations in cancer‐related genes selectively target hinge‐neighboring residues that orchestrate collective structural dynamics. To test our hypothesis, we selected 69 cancer‐related genes from the Cancer Gene Census database and their representative protein structures from the Protein Data Bank. We first identified the hinge residues in two global modes of motion by applying the Gaussian Network Model. We then showed that missense mutations are significantly enriched on hinge‐neighboring residues in oncogenes and tumor suppressor genes. We observed that several oncogenes (eg, MAP2K1, PTPN11, and KRAS) and tumor suppressor genes (eg, EZH2, CDKN2C, and RHOA) strongly exhibit this phenomenon. This study highlights and rationalizes the functional importance of missense mutations on hinge‐neighboring residues in cancer.