Exploring Methods of Extraction of Cluster Free Energy from Small-N Molecular Dynamics Simulations Restricted; Files Only

Zhang, Xiaokun (Summer 2021)

Permanent URL: https://etd.library.emory.edu/concern/etds/6q182m326?locale=en


Molecular dynamics simulations provide us a powerful tool to study the microscopic properties of reversible aggregates. However, the simulations often do not represent the behavior of a macroscopic system of aggregation due to the limit of system size. This dissertation will show (1) the establishment of fast and reliable analysis tools to extract thermodynamic properties from canonical ensemble simulations of small systems undergoing reversible aggregation and (2) example applications of these tools for micellizations of amphiphilic surfactants, including size-dependent cluster free energy, critical micelle concentration, micelle size, and predictions of X-ray scattering profiles. The tools are based on the "Partition-Enabled Analysis of Cluster Histograms" (PEACH) approach. A dramatic reduction in computational time for analysis is achieved through a strategy similar to the "selector variable method". With PEACH method and enthalpy change calculations, we explored the temperature-related cluster free energy and derived enthalpy change for micellization of sodium octanoate. The enthalpograms generated from simulation data were consistent with results from isothermal titration calorimetry experiments1. Molecular dynamics (MD) simulations of the zwitterionic surfactant octyl phosphocholine (OPC) in water have been performed with two force fields. Micelle size distributions from a number of trajectories were analyzed using the PEACH method to yield free energies of aggregation for premicelles and micelles over the full range from 2 to over 40 molecules. The dependence of free energy on aggregation number was consistent with the functional form derived from the “quasi-droplet” model of micellization. PEACH- BAR method was proposed to extract the free energy of aggregation vs. aggregate size systems with slow dissociation rate and low critical micelle concentration (CMC of approximately 1-2 mM) and applied to a united atom model of the surfactant dodecyl phosphocholine (DPC) in water. The new approach applies PEACH to a model with weakened attractions between aggregants, which allows sampling of a continuous range of cluster sizes, then recovers the free energy of aggregation under the original fully-attractive force field using the BAR free energy difference method. 

Table of Contents

Chapter 1 Introduction

Chapter 2 Extracting aggregation free energies of mixed clusters from simulations of small systems: application to ionic surfactant micelles

2.1 Introduction

2.2 Theory and algorithm development

2.3 Simulation and analysis details

2.4 Results and discussion

2.5 Conclusions

Chapter 3. Derivation of micelle size-dependent free energies of aggregation for octyl phosphocholine from molecular dynamics simulation

3.1 Introduction

3.2 Methods

3.3 Results and Discussion

3.4 Conclusions

3.5 Acknowledgments

Chapter 4 Free Energy of Micellization of Dodecyl Phosphocholine (DPC) from Molecular Simulation: Hybrid PEACH-BAR Method

4.1 Introduction

4.2 Method

4.3 Results and Discussions

4.4 Conclusions

4.5 Acknowledgments

Chapter 5. Study of Enthalpy Change for Micellization of Sodium Octanoate

5.1 Introduction

5.2 Methods

5.3 Results

5.4 Conclusions

Appendix I. Bayesian optimization method

Appendix II. Supporting Information for Chapter 2

Appendix III. Supporting Information for Chapter 3

Appendix IV. Supporting Information for Chapter 4


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