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Anjela Manandhar

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Papers by Anjela Manandhar

Research paper thumbnail of The interaction of supramolecular anticancer drug amphiphiles with phospholipid membranes

Nanoscale Advances, 2021

Molecular dynamics simulations probe drug delivery vehicle-membrane interaction.

Research paper thumbnail of Sequence Dependent Barriers to Nucleosome Unwrapping

Biophysical Journal, 2021

Research paper thumbnail of Rational Coarse-Grained Molecular Dynamics Simulations of Supramolecular Anticancer Nanotubes

The Journal of Physical Chemistry B, 2019

Peptide self-assembly has been used to design an array of nanostructures that possess functional ... more Peptide self-assembly has been used to design an array of nanostructures that possess functional biomedical applications. Experimental studies have reported nanofilament and nanotube formation from peptide-based drug amphiphiles (DAs). These DAs have shown to possess an inherently high drug loading with a tunable release mechanism. Herein we report rational coarse grained molecular dynamics simulations of the self-assembly process and the structure and stability of pre-assembled nanotubes at longer time scales (s). We find aggregation between these DAs is at the sub-microsecond time scale is driven by directional aromatic interactions between the drugs. The drugs form a large and high-density nucleus that is stable throughout microsecond time scales. Simulations of nanotubes characterize the drug-drug stacking and find correlations at nm length-scales. These simulations can inform the rational molecular design of drug amphiphiles.

Research paper thumbnail of Effect of Nucleotide State on the Protofilament Conformation of Tubulin Octamers

The journal of physical chemistry. B, Jan 6, 2018

At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule ... more At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule (MT) is driven by the nucleotide state (GTP vs GDP) in the β subunit of the tubulin dimers at the MT cap. Here, we use large-scale molecular dynamics (MD) simulations and normal-mode analysis (NMA) to characterize the effect of a single GTP cap layer on tubulin octamers composed of two neighboring protofilaments (PFs). We utilize recently reported high-resolution structures of dynamic MTs to simulate a GDP octamer both with and without a single GTP cap layer. We perform multiple replicas of long-time atomistic MD simulations (3 replicas, 0.3 μs for each replica, 0.9 μs for each octamer system, and 1.8 μs total) of both octamers. We observe that a single GTP cap layer induces structural differences in neighboring PFs, finding that one PF possesses a gradual curvature, compared to the second PF which possesses a kinked conformation. This results in either curling or splaying between these ...

Research paper thumbnail of Molecular simulations of peptide amphiphiles

Org. Biomol. Chem., 2017

This review describes recent progress in the area of molecular simulations of peptide assemblies,... more This review describes recent progress in the area of molecular simulations of peptide assemblies, including peptide-amphiphiles, and drug-amphiphiles.

Research paper thumbnail of Targeting SARS-CoV-2 M3CLpro by HCV NS3/4a Inhibitors: In Silico Modeling and In Vitro Screening

Journal of Chemical Information and Modeling, 2021

Research paper thumbnail of Redetermination and absolute configuration of (+)-7-epiclusianone

Acta Crystallographica Section E Structure Reports Online, 2012

Research paper thumbnail of The interaction of supramolecular anticancer drug amphiphiles with phospholipid membranes

Nanoscale Advances, 2021

Molecular dynamics simulations probe drug delivery vehicle-membrane interaction.

Research paper thumbnail of Sequence Dependent Barriers to Nucleosome Unwrapping

Biophysical Journal, 2021

Research paper thumbnail of Rational Coarse-Grained Molecular Dynamics Simulations of Supramolecular Anticancer Nanotubes

The Journal of Physical Chemistry B, 2019

Peptide self-assembly has been used to design an array of nanostructures that possess functional ... more Peptide self-assembly has been used to design an array of nanostructures that possess functional biomedical applications. Experimental studies have reported nanofilament and nanotube formation from peptide-based drug amphiphiles (DAs). These DAs have shown to possess an inherently high drug loading with a tunable release mechanism. Herein we report rational coarse grained molecular dynamics simulations of the self-assembly process and the structure and stability of pre-assembled nanotubes at longer time scales (s). We find aggregation between these DAs is at the sub-microsecond time scale is driven by directional aromatic interactions between the drugs. The drugs form a large and high-density nucleus that is stable throughout microsecond time scales. Simulations of nanotubes characterize the drug-drug stacking and find correlations at nm length-scales. These simulations can inform the rational molecular design of drug amphiphiles.

Research paper thumbnail of Effect of Nucleotide State on the Protofilament Conformation of Tubulin Octamers

The journal of physical chemistry. B, Jan 6, 2018

At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule ... more At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule (MT) is driven by the nucleotide state (GTP vs GDP) in the β subunit of the tubulin dimers at the MT cap. Here, we use large-scale molecular dynamics (MD) simulations and normal-mode analysis (NMA) to characterize the effect of a single GTP cap layer on tubulin octamers composed of two neighboring protofilaments (PFs). We utilize recently reported high-resolution structures of dynamic MTs to simulate a GDP octamer both with and without a single GTP cap layer. We perform multiple replicas of long-time atomistic MD simulations (3 replicas, 0.3 μs for each replica, 0.9 μs for each octamer system, and 1.8 μs total) of both octamers. We observe that a single GTP cap layer induces structural differences in neighboring PFs, finding that one PF possesses a gradual curvature, compared to the second PF which possesses a kinked conformation. This results in either curling or splaying between these ...

Research paper thumbnail of Molecular simulations of peptide amphiphiles

Org. Biomol. Chem., 2017

This review describes recent progress in the area of molecular simulations of peptide assemblies,... more This review describes recent progress in the area of molecular simulations of peptide assemblies, including peptide-amphiphiles, and drug-amphiphiles.

Research paper thumbnail of Targeting SARS-CoV-2 M3CLpro by HCV NS3/4a Inhibitors: In Silico Modeling and In Vitro Screening

Journal of Chemical Information and Modeling, 2021

Research paper thumbnail of Redetermination and absolute configuration of (+)-7-epiclusianone

Acta Crystallographica Section E Structure Reports Online, 2012

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