Simulating Transport Across the Blood-Brain Barrier Endothelial Membrane: Comparing Unbiased Molecular Dynamics Methods to Enhanced Sampling Protocols.
- 1School of Medicine, Pharmacy and Biomedical Sciences, Faculty of Science & Health, University of Portsmouth, Portsmouth PO1 2DT, UK.
- 2Institute for Life Sciences and Health, University of Portsmouth, Portsmouth PO1 2DT, UK.
Abstract
The blood-brain barrier (BBB) is a highly selective membrane that restricts the delivery of therapeutics into the brain. In this review, we consider a number of computational techniques that can be used to assess BBB transport and central nervous system (CNS) delivery. We outline the details of human brain microvascular endothelial cells (hBMECs) and how passive transport is the main mode of transport. We then outline details of molecular dynamics techniques for predicting in silico drug permeability across an atomistic hBMEC model. Due to the very slow timescales required to sample CNS transport a priori, we compare transition-based counting (TBC) methodology to enhanced sampling techniques. These advanced methods overcome traditional sampling limitations and include umbrella sampling (US) with the Weighted Histogram Analysis Method (WHAM) and the Dynamic Histogram Analysis Method (DHAM). Additionally, we consider constant velocity-steered molecular dynamics (cv-SMD)/US combined with the Inhomogeneous Solubility-Diffusion (ISD) model, as well as Metadynamics and the Adaptive Biasing Force.
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BibTeX
@article{oluwasegun2026simulating,
title = {{Simulating Transport Across the Blood-Brain Barrier Endothelial Membrane: Comparing Unbiased Molecular Dynamics Methods to Enhanced Sampling Protocols.}},
author = {Jerry Oluwasegun and Ben William Franey and Christian Jorgensen},
journal = {Membranes},
year = {2026},
month = oct,
doi = {10.3390/membranes16100343},
url = {https://europepmc.org/article/MED/42931021},
note = {CC BY},
}
RIS
TY - JOUR
TI - Simulating Transport Across the Blood-Brain Barrier Endothelial Membrane: Comparing Unbiased Molecular Dynamics Methods to Enhanced Sampling Protocols.
AU - Jerry Oluwasegun
AU - Ben William Franey
AU - Christian Jorgensen
PY - 2026
DA - 2026/10/16
JO - Membranes
DO - 10.3390/membranes16100343
UR - https://europepmc.org/article/MED/42931021
AB - The blood-brain barrier (BBB) is a highly selective membrane that restricts the delivery of therapeutics into the brain. In this review, we consider a number of computational techniques that can be used to assess BBB transport and central nervous system (CNS) delivery. We outline the details of human brain microvascular endothelial cells (hBMECs) and how passive transport is the main mode of transport. We then outline details of molecular dynamics techniques for predicting in silico drug permeability across an atomistic hBMEC model. Due to the very slow timescales required to sample CNS transport a priori, we compare transition-based counting (TBC) methodology to enhanced sampling techniques. These advanced methods overcome traditional sampling limitations and include umbrella sampling (US) with the Weighted Histogram Analysis Method (WHAM) and the Dynamic Histogram Analysis Method (DHAM). Additionally, we consider constant velocity-steered molecular dynamics (cv-SMD)/US combined with the Inhomogeneous Solubility-Diffusion (ISD) model, as well as Metadynamics and the Adaptive Biasing Force.
SN - 2077-0375
ER -