Work Package 3

Objectives: Simulation of curved and assymetric membranes

• Task 1: Construction of models of asymmetric membranes with tunable curvature, lipid and cholesterol content.
• Task 2: Determination of potentials of means force for translocating Pt and Au-based drugs through these models of membranes
• Task 3: Training specific to MD methods and development of softwares used for trajectory analysis
• Task 4: Insertion of membrane proteins into the membranes with different curvature. Protein equilibration and determination of the conformational changes cause by the membrane environment.

Dissemination

1. “Interaction of C 60 fullerenes with asymmetric and curved lipid membranes: a molecular dynamics study”, Physical Chemistry Chemical Physics 18 (1), 278-284.
2. “Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery”, Nature Communications, 2017, DOI: 10.1038/ncomms15678.
3. “The influence of curvature on the properties of the plasma membrane. Insights from atomistic molecular dynamics simulations” – submitted to Nature Scientific Reports

Finished tasks

• Model of the mammalian plasma membrane with enforced curvature is built. All accompanying methodology and software is developed and tested.
• Methodology of computing the potentials of means forces (PMFs) across curved membranes is developed and tested.
• PMFs of the simple small hydrophilic and hydrophobic compounds (ions, water, benzene) are computed.
• Paper describing these findings are submitted to Nature Scientific Reports (currently under review).

Work in progress:

• PMFs of the Pt-based drugs in curved membranes of different composition.
• Simulations of the membranes mimicking composition of cancer cells (PS exposure).

Publications in Nature-level journals are rare in Ukraine.

The content of our Nature comm. paper was adapted for wider audience and disseminated at the web site of NAS of Ukraine (for academic researchers and general public) and in the journal “Health of Ukraine” (for wide community of health-care professionals and medical researchers).

The salient features of this paper were also disseminated in France through an article published the french national “Journal du Dimanche” (http://www.lejdd.fr/societe/sciences/des-nanomedicaments-pour-soigner-les-cancer-3358973)