Multiscale modeling of keratin, collagen, elastin and related human diseases: Perspectives from atomistic to coarse-grained molecular dynamics simulations

Jingjie Yeo, Gang Seob Jung, Anna Tarakanova, Francisco J. Martín-Martínez, Zhao Qin, Yuan Cheng, Yong Wei Zhang, Markus J. Buehler

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)112-124
Number of pages13
JournalExtreme Mechanics Letters
StatePublished - Apr 2018
Externally publishedYes


  • Collagen
  • Defect
  • Elasticity
  • Elastin
  • Failure
  • Human disease phenotypes
  • Keratin
  • Mechanics
  • Mechanobiology
  • Molecular dynamics
  • Mutation

ASJC Scopus subject areas

  • Bioengineering
  • Chemical Engineering (miscellaneous)
  • Engineering (miscellaneous)
  • Mechanics of Materials
  • Mechanical Engineering


Dive into the research topics of 'Multiscale modeling of keratin, collagen, elastin and related human diseases: Perspectives from atomistic to coarse-grained molecular dynamics simulations'. Together they form a unique fingerprint.

Cite this