Molecular dynamics simulation of amphiphilic aggregates

In this dissertation, molecular dynamics simulations were performed for systems containing amphiphilic aggregates, such as monolayers, bilayers, and reverse micelles. Various analysis methods were used in order to investigate structural and dynamical properties and solve particular problems for different systems. First, we present simulations where we observed successful self-assembly of reverse micelles in a three-component system containing supercritical CO2, water, and fluorinated surfactant starting from random configurations. Such self-assembly allows for the future computational study of structural and thermodynamic properties of microemulsions in water/CO2 systems that will be less dependent on the initial conditions. Next, a series of molecular dynamics simulations were performed to study the PFPE (perfluoropolyether) and PE (polyether) surfactant monolayers and micelles at the water/supercritical carbon dioxide interface. We observed that values of intramolecular bonded interaction parameters which are related to chain rigidity determine the monolayer surface pressure. We show that good and bad properties of PFPE/PE surfactants are connected to conformational entropy. In order to study the effect of the hydration force, we simulated systems with model hydrophilic plates. We studied the effect of charge correlation on the potential of mean force between plates. The orientational structure of water between the plates was investigated to understand the effect of molecular structure of water on the properties of the potential of mean force. Finally, we calculated the free energy cost for removing a cholesterol molecule from two different lipid bilayers. The results can help us to understand the relationship between the lipid structure and the lipid-cholesterol affinity. N-palmitoyl-sphingomyelin was found to have a better cholesterol affinity compared with that of phosphatidylcholine lipid DPPC, according to our free energy values from molecular dynamics simulations

Multiscale Coarse-Graining of the Protein Energy Landscape

A variety of coarse-grained (CG) models exists for simulation of proteins. An outstanding problem is the construction of a CG model with physically accurate conformational energetics rivaling all-atom force fields. In the present work, atomistic simulations of peptide folding and aggregation equilibria are force-matched using multiscale coarse-graining to develop and test a CG interaction potential of general utility for the simulation of proteins of arbitrary sequence. The reduced representation relies on multiple interaction sites to maintain the anisotropic packing and polarity of individual sidechains. CG energy landscapes computed from replica exchange simulations of the folding of Trpzip, Trp-cage and adenylate kinase resemble those of other reduced representations; non-native structures are observed with energies similar to those of the native state. The artifactual stabilization of misfolded states implies that non-native interactions play a deciding role in deviations from ideal funnel-like cooperative folding. The role of surface tension, backbone hydrogen bonding and the smooth pairwise CG landscape is discussed. Ab initio folding aside, the improved treatment of sidechain rotamers results in stability of the native state in constant temperature simulations of Trpzip, Trp-cage, and the open to closed conformational transition of adenylate kinase, illustrating the potential value of the CG force field for simulating protein complexes and transitions between well-defined structural states.</p

Multiscale Coarse-Graining of the Protein Energy Landscape

A variety of coarse-grained (CG) models exists for simulation of proteins. An outstanding problem is the construction of a CG model with physically accurate conformational energetics rivaling all-atom force fields. In the present work, atomistic simulations of peptide folding and aggregation equilibria are force-matched using multiscale coarse-graining to develop and test a CG interaction potential of general utility for the simulation of proteins of arbitrary sequence. The reduced representation relies on multiple interaction sites to maintain the anisotropic packing and polarity of individual sidechains. CG energy landscapes computed from replica exchange simulations of the folding of Trpzip, Trp-cage and adenylate kinase resemble those of other reduced representations; non-native structures are observed with energies similar to those of the native state. The artifactual stabilization of misfolded states implies that non-native interactions play a deciding role in deviations from ideal funnel-like cooperative folding. The role of surface tension, backbone hydrogen bonding and the smooth pairwise CG landscape is discussed. Ab initio folding aside, the improved treatment of sidechain rotamers results in stability of the native state in constant temperature simulations of Trpzip, Trp-cage, and the open to closed conformational transition of adenylate kinase, illustrating the potential value of the CG force field for simulating protein complexes and transitions between well-defined structural states

Data for Investigating The Protein Phase Behavior In Polarized Fungal Growth By Coarse-Grained Molecular Simulation

Final research data for MOE Tier 1 grant 2018-T1-001-096

PRE data for "Structure Ensemble of the First Two RNA Recognition Motif Domains of a Poly(U) Binding Protein from Paramagnetic Relaxation Enhancement and Molecular Simulation"

<br> <p><b>Structure Ensemble of the First Two </b><b>RNA Recognition Motif</b><b> Domains of a Poly(U) Binding Protein from Paramagnetic Relaxation Enhancement and Molecular Simulation</b></p> <p><b> </b></p> <p>Guanhua Zhu¹, Wei Liu², Chenglong Bao³, Dudu Tong¹, Hui Ji³, Zuowei Shen³, Daiwen Yang², Lanyuan Lu^1*</p><p>^{Manuscript submitted for review.}</p