Programme

P.1 -- Poster, VCTP-45

Date: Tuesday, 13 October 2020

Time: 08:30 - 10:00

Fast Estimation of the Blood-Brain Barrier Permeability by Pulling a Ligand through a Lipid Membrane

Nguyen Quoc Thai (1), Panagiotis E. Theodorakis (2), Huynh Thi Ngoc Thanh (1), Mai Suan Li (2)

(1) Dong Thap University, 783 Pham Huu Lau Street, Ward 6, Cao Lanh City, Dong Thap, Vietnam; (2) Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw, Poland.

The blood-brain barrier (BBB) is the physical barrier that regulates the homeostasis of the neural microenvironment. A relative estimate of the BBB permeability, which is important for drug design, may be experimentally provided by the logBB (the blood – brain concentration ratio) and the logPS (permeability – surface-area product), while many computational methods aim to identify key properties that correlate well with these quantities. Here, we use steered molecular dynamics simulation to estimate the BBB permeability of various compounds on the basis of simple lipid-membrane models by computing the nonequilibrium work, $W_{neq}$, produced by pulling the compounds through the membrane. We found that the values of $W_{neq}$ correlate remarkably well with logBB and logPS for a range of compounds and pulling speeds. Moreover, our results provide insight into the role of hydrogen bonds, the energetic barriers on the ligands during their pulling. Our method is computationally easy to implement and fast. Therefore, we anticipate that it could provide a reliable pre-screening tool for estimating the relative permeability of the BBB to various substances.

Presenter: Nguyen Quoc Thai

Presentation file: