Linking 3D and 2D binding kinetics of membrane proteins by multiscale simulations

Zhong Ru Xie, Jiawen Chen, Yinghao Wu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Membrane proteins are among the most functionally important proteins in cells. Unlike soluble proteins, they only possess two translational degrees of freedom on cell surfaces, and experience significant constraints on their rotations. As a result, it is currently challenging to characterize the in situ binding of membrane proteins. Using the membrane receptors CD2 and CD58 as a testing system, we developed a multiscale simulation framework to study the differences of protein binding kinetics between 3D and 2D environments. The association and dissociation processes were implemented by a coarse-grained Monte-Carlo algorithm, while the dynamic properties of proteins diffusing on lipid bilayer were captured from all-atom molecular dynamic simulations. Our simulations show that molecular diffusion, linker flexibility and membrane fluctuations are important factors in adjusting binding kinetics. Moreover, by calibrating simulation parameters to the measurements of 3D binding, we derived the 2D binding constant which is quantitatively consistent with the experimental data, indicating that the method is able to capture the difference between 3D and 2D binding environments. Finally, we found that the 2D dissociation between CD2 and CD58 is about 100-fold slower than the 3D dissociation. In summary, our simulation framework offered a generic approach to study binding mechanisms of membrane proteins.

Original languageEnglish (US)
Pages (from-to)1789-1799
Number of pages11
JournalProtein Science
Volume23
Issue number12
DOIs
StatePublished - Dec 1 2014

Fingerprint

Membrane Proteins
Kinetics
Membranes
Proteins
Lipid bilayers
Lipid Bilayers
Molecular Dynamics Simulation
Protein Binding
Molecular dynamics
Carrier Proteins
Association reactions
Atoms
Computer simulation
Testing

Keywords

  • binding kinetics
  • coarse-grained model
  • membrane proteins
  • multiscale simulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Linking 3D and 2D binding kinetics of membrane proteins by multiscale simulations. / Xie, Zhong Ru; Chen, Jiawen; Wu, Yinghao.

In: Protein Science, Vol. 23, No. 12, 01.12.2014, p. 1789-1799.

Research output: Contribution to journalArticle

Xie, Zhong Ru ; Chen, Jiawen ; Wu, Yinghao. / Linking 3D and 2D binding kinetics of membrane proteins by multiscale simulations. In: Protein Science. 2014 ; Vol. 23, No. 12. pp. 1789-1799.
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