Unfolding of titin domains studied by molecular dynamics simulations

Mu Gao, Hui Lu, Klaus Schulten

Research output: Contribution to journalArticlepeer-review


Titin, a ∼1 μm long protein found in striated muscle myofibrils, possesses unique elastic properties. The extensible behavior of titin has been demonstrated in atomic force microscopy and optical tweezer experiments to involve the reversible unfolding of individual immunoglobulin-like (Ig) domains. We have used steered molecular dynamics (SMD), a novel computer simulation method, to investigate the mechanical response of single titin Ig domains upon stress. Simulations of stretching Ig domains I1 and I27 have been performed in a solvent of explicit water molecules. The SMD approach provides a detailed structural and dynamic description of how Ig domains react to external forces. Validation of SMD results includes both qualitative and quantitative agreement with AFM recordings. Furthermore, combining SMD with single molecule experimental data leads to a comprehensive understanding of Ig domains' mechanical properties. A set of backbone hydrogen bonds that link the domains' terminal β-strands play a key role in the mechanical resistance to external forces. Slight differences in architecture permit a mechanical unfolding intermediate for I27, but not for I1. Refolding simulations of I27 demonstrate a locking mechanism.

Original languageEnglish (US)
Pages (from-to)513-521
Number of pages9
JournalJournal of Muscle Research and Cell Motility
Issue number5-6
StatePublished - 2002

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cell Biology


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