Determination of Base Flipping Free Energy Landscapes from Nonequilibrium Stratification

21 March 2019, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Correct calculation of the variation of free energy upon base flipping is crucial in understanding the dynamics of DNA systems. The free energy landscape along the flipping pathway gives the thermodynamic stability and the flexibility of base-paired states. Although numerous free energy simulations are performed in the base flipping cases, no theoretically rigorous nonequilibrium techniques are devised and employed to investigate the thermodynamics of base flipping. In the current work, we report a general nonequilibrium stratification scheme for efficient calculation of the free energy landscape of base flipping in DNA duplex. We carefully monitor the convergence behavior of the equilibrium sampling based free energy simulation and the nonequilibrium stratification and determine the empirical length of time blocks required for converged sampling. Comparison between the performances of equilibrium umbrella sampling and nonequilibrium stratification is given. The results show that nonequilibrium free energy simulation is able to give similar accuracy and efficiency compared with the equilibrium enhanced sampling technique in the base flipping cases. We further test a convergence criterion we previously proposed and it comes out that the convergence behavior determined by this criterion agrees with those given by the time-invariant behavior of PMF and the nonlinear dependence of standard deviation on the sample size.

Keywords

Free Energy Landscapes
DNA
Base Flipping
Steered Molecular Dynamics
Free Energy Simulation
Bennett Acceptance Ratio
Weighted Histogram Analysis Methods
Nonequilibrium Work Methods
Collective Variable
Periodic CV
Free Energy Perturbation
Bidirectional pulling
Statistical Inefficiency
Autocorrelation
Convergence Criterion
Stiff spring limit
Force Field Comparison
AMBER Force Fields
OL15
bsc1
Sample Size
Standard Deviation
Phase Space Overlap
Reweighting

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.