COARSE-GRAINED MODELING OF PROTEIN UNFOLDING DYNAMICS
Mingge Deng1, George Em Karniadakis1
1Division of Applied Mathematics, Brown University, Providence, RI 02912.
Multiscale Modeling & Simulation : a SIAM Interdisciplinary Journal
|November 18, 2014
Summary
We developed a dynamic elastic network model (DENM) to simulate protein unfolding under force. This model accurately predicts protein dynamics, showing native structure dictates overall unfolding behavior.
Area of Science:
- Biophysics
- Computational Biology
- Structural Biology
Background:
- Protein unfolding is crucial for understanding protein function and disease.
- Simulating protein mechanical properties requires accurate modeling of complex interactions.
Purpose of the Study:
- To introduce a novel dynamic elastic network model (DENM) for simulating force-induced protein unfolding.
- To investigate how native protein structure influences large-scale unfolding dynamics.
Main Methods:
- Constructed protein interaction networks from Protein Data Bank structures.
- Modeled noncovalent bond breaking using Kramer's theory and Bell's model.
- Employed coarse-graining and validated against molecular dynamics simulations.
Main Results:
- DENM accurately captures the force-extension processes of Fibrinogen and Titin.
- The native protein structure fundamentally determines the complete unfolding pathway.
- Model shows protein dynamics are not limited to fluctuations around the native state.
Conclusions:
- DENM provides a robust and efficient method for studying protein mechanical properties.
- Understanding protein unfolding dynamics is essential for drug design and protein engineering.
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