Stretching Biomolecules

Biomolecular self-assembly is the complicated processes characterized by broad and hierarchical structure of energy, length, and time scales. Various experimental tools have, for decades, been used to understand the principles governing the dynamics of biomolecular systems. The recent advent of single molecule force experiments has expanded our perspective on the energetics of biomolecules, explicitly showing the diverse traces of the individual molecules undergoing heterogeneous processes. Based on theoretical arguments and Langevin dynamics simulations of coarse-grained models, I suggest that the following aspects of biomolecules can be elucidated through the force experiments…

Contents

1 Introduction
1.1 Protein/RNA folding
1.2 Force as a variable in single molecule experiments
1.3 Brief summary of force experiments on proteins and RNA
1.4 Theoretical background
1.5 Computational background
1.6 Overview
2 Measuring energy landscape roughness of proteins and RNA using mechanical unfolding experiments
2.1 Introduction
2.2 Caricature of energy landscape of RNA and proteins
2.3 Unfolding at constant force
2.4 Stretching at constant loading rate
2.5 Numerical results
2.6 Proposed experiments
2.7 Conclusions
3 Mechanical unfolding of RNA hairpins
3.1 Introduction
3.2 Methods
3.2.1 Hairpin sequence
3.2.2 Model
3.2.3 Simulations
3.2.4 Phase diagram and free energy profile
3.3 Results and Discussion
3.3.1 Determination of the Native state
3.3.2 Force-temperature (f,T) phase diagram
3.3.3 Two state dynamics and equilibrium
3.3.4 Cooperativity of unfolding depends on force
3.3.5 Time scales of hopping transition
3.3.6 Unfolding dynamics at constant force
3.3.7 Refolding under force quench
3.3.8 Force quench refolding occurs in multiple stages
3.4 Conclusion
4 Investigation on forced unfolding and refolding of RNA hairpins from force propagation and energy landscape perspective
4.1 Introduction
4.2 Methods
4.2.1 Force simulations at constant pulling speed
4.2.2 Force simulations in the presence of linker
4.3 Results and Discussion
4.3.1 Factors a®ecting stretching experiment
4.3.2 Thermal Unfolding and Forced Unfolding
4.3.3 Hammond postulate for force-unfolding experiments
4.3.4 Refolding dynamics from stretched state
4.4 Conclusions
5 Predicting force-induced unfolding pathways of biomolecules using a topologybased model
5.1 Introduction
5.2 Method
5.2.1 Topology model
5.3 Results and Discussions
5.3.1 Stretching Tetrahymena thermophila ribozyme
5.3.2 Pulling speed dependent unfolding pathways
5.3.3 Refolding
5.4 Conclusions
A Identi¯cation of force peak through comparison between force and contact rupture as a function of time
B Contact rupture history of Azoarcus ribozyme at varying loading rates
Bibliography

Author: Hyeon, Changbong

Source: University of Maryland

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