Study of protein structural deformations under external mechanical perturbations by a coarse-grained simulation method

Jiawen Chen, Zhong Ru Xie, Yinghao Wu

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


The mechanical properties of biomolecules play pivotal roles in regulating cellular functions. For instance, extracellular mechanical stimuli are converted to intracellular biochemical activities by membrane receptors and their downstream adaptor proteins during mechanotransduction. In general, proteins favor the conformation with the lowest free energy. External forces modify the energy landscape of proteins and drive them to unfolded or deformed conformations that are of functional relevance. Therefore, the study of the physical properties of proteins under external forces is of fundamental importance to understand their functions in cellular mechanics. Here, a coarse-grained computational model was developed to simulate the unfolding or deformation of proteins under mechanical perturbation. By applying this method to unfolding of previously studied proteins or protein fragments with external forces, we demonstrated that our results are quantitatively comparable to previous experimental or all-atom computational studies. The model was further extended to the problem of elastic deformation of large protein complexes formed between membrane receptors and their ligands. Our studies of binding between T cell receptor (TCR) and major histocompatibility complex (MHC) illustrated that stretching of MHC ligand initially lowers its binding energy with TCR, supporting the recent experimental report that TCR/MHC complex is formed through the catch-bond mechanism. Finally, the method was, for the first time, applied to pulling of an eight-cadherin cluster that was formed by their trans and cis binding interfaces. Our simulation results show that mechanical properties of adherens junctions are functionally important to cell adhesion.

Original languageEnglish (US)
Pages (from-to)317-329
Number of pages13
JournalBiomechanics and Modeling in Mechanobiology
Issue number2
StatePublished - Apr 1 2016


  • Cell adhesion
  • Coarse-grained simulation
  • Mechanotransduction

ASJC Scopus subject areas

  • Biotechnology
  • Modeling and Simulation
  • Mechanical Engineering


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