Multiscale modeling of keratin, collagen, elastin and related human diseases: Perspectives from atomistic to coarse-grained molecular dynamics simulations
| Autor: | Yong-Wei Zhang, Markus J. Buehler, Zhao Qin, Jingjie Yeo, Yuan Cheng, Gang Seob Jung, Francisco J. Martin-Martinez, Anna Tarakanova |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification biology Mechanical Engineering Scleroprotein Bioengineering Computational biology medicine.disease Multiscale modeling Epidermolytic hyperkeratosis Article 03 medical and health sciences Mechanobiology 030104 developmental biology chemistry Mechanics of Materials Keratin medicine biology.protein Chemical Engineering (miscellaneous) Alport syndrome Engineering (miscellaneous) Elastin Cutis laxa |
| Zdroj: | Extreme Mech Lett |
| ISSN: | 2352-4316 |
| Popis: | Scleroproteins are an important category of proteins within the human body that adopt filamentous, elongated conformations in contrast with typical globular proteins. These include keratin, collagen, and elastin, which often serve a common mechanical function in structural support of cells and tissues. Genetic mutations alter these proteins, disrupting their functions and causing diseases. Computational characterization of these mutations has proven to be extremely valuable in identifying the intricate structure-function relationships of scleroproteins from the molecular scale up, especially if combined with multiscale experimental analysis and the synthesis of model proteins to test specific structure-function relationships. In this work, we review numerous critical diseases that are related to keratin, collagen, and elastin, and through several case studies, we propose ways of extensively utilizing multiscale modeling, from atomistic to coarse-grained molecular dynamics simulations, to uncover the molecular origins for some of these diseases and to aid in the development of novel cures and therapies. As case studies, we examine the effects of the genetic disease Epidermolytic Hyperkeratosis (EHK) on the structure and aggregation of keratins 1 and 10; we propose models to understand the diseases of Osteogenesis Imperfecta (OI) and Alport syndrome (AS) that affect the mechanical and aggregation properties of collagen; and we develop atomistic molecular dynamics and elastic network models of elastin to determine the role of mutations in diseases such as Cutis Laxa and Supravalvular Aortic Stenosis on elastin's structure and molecular conformational motions and implications for assembly. |
| Databáze: | OpenAIRE |
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