Intrinsically disordered proteins by homology modeling and replica exchange molecular dynamics simulations: A case study of amyloid-?42
Yükleniyor...
Tarih
2024
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Homology modeling emerges as a potent tool unveiling the structural enigma of intrinsically disordered proteins (IDPs), with recent advancements such as AlphaFold2 enhancing the precision of these analyses. The process usually involves identifying homologous proteins with known structures and utilizing their templates to predict the three-dimensional architecture of the target IDP. However, IDPs lack a welldefined three-dimensional structure, and their flexibility makes it difficult to predict their conformations accurately. On the other hand, special sampling molecular dynamics simulations have been shown to be useful in defining the distinct structural properties of IDPs. Here, the structural properties of the disordered amyloid-?42 peptide were predicted using various homology modeling tools, including C-I-TASSER, ITASSER, Phyre2, SwissModel, and AlphaFold2. In parallel, extensive replica exchange molecular dynamics simulations of A?42 were conducted. Results from homology modeling were compared to our replica exchange molecular dynamics simulations and experiments to gain insights into the accuracy of homology modeling tools for IDPs used in this work. Based on our findings, none of the homology modeling tools used in this work can fully capture the structural properties of A?42. However, C-I-TASSER yields a radius of gyration and tertiary structure properties that are more in accord with the simulations and experimental data rather than I-TASSER, Phyre2, SwissModel, and AlphaFold2.
Açıklama
Anahtar Kelimeler
Intrinsically disordered proteins, Amyloid-β42, Homology modeling, Replica exchange molecular dynamics simulations
Kaynak
Journal of the Turkish Chemical Society
WoS Q Değeri
Scopus Q Değeri
Cilt
11
Sayı
3
Künye
Coskuner Weber O. (2024). Intrinsically disordered proteins by homology modeling and replica exchange molecular dynamics simulations: A case study of amyloid-?42. Journal of the Turkish Chemical Society.11(3):1151-1164.
