Multiscale physics-based in silico modelling of nanocarrier-assisted intravascular drug delivery

A rational design of drug nanocarriers supported by in silico modelling tools can improve the efficacy of nanosystem-based intravascular drug delivery (IVDD). Computational model development stems from the vision of replacing conventional (pre)clinical trials with advanced simulations and applies to the development of more efficient nanocarriers for intravascular therapies. To establish a standardized framework for in silico preclinical trials, it is necessary to include in silico tools that can model each experimental stage of a preclinical trial for a respective nanocarrier system and give accurate and verifiable results. This review paper highlights the status of intravascular drug delivery supported by nanocarriers and discusses the modelling stages of a physics-based multiscale modelling framework that should be developed, validated and exploited to address the need for an effective preclinical assessment of nanocarriers for IVDD

Note : Network random walk model of two-state protein folding : Test of the theory

We study two-state protein folding in the framework of a toy model of protein dynamics. This model has an important advantage: it allows for an analytical solution for the sum of folding and unfolding rate constants [A. M. Berezhkovskii, F. Tofoleanu, and N.-V. Buchete, J. Chem. Theory Comput. 7, 2370 (2011)10.1021/ct200281d] and hence for the reactive flux at equilibrium. We use the model to test the Kramers-type formula for the reactive flux, which was derived assuming that the protein dynamics is described by a Markov random walk on a network of complex connectivity [A. Berezhkovskii, G. Hummer, and A. Szabo, J. Chem. Phys. 130, 205102 (2009)10.1063/1.3139063]. It is shown that the Kramers-type formula leads to the same result for the reactive flux as the sum of the rate constants.AM