Recent advances on molecular dynamics-based techniques to address drug membrane permeability with atomistic detail

André M M Gomes; Paulo J Costa; Miguel Machuqueiro

doi:10.1016/j.bbadva.2023.100099

Recent advances on molecular dynamics-based techniques to address drug membrane permeability with atomistic detail

BBA Adv. 2023 Aug 16:4:100099. doi: 10.1016/j.bbadva.2023.100099. eCollection 2023.

Authors

André M M Gomes^{1

2}, Paulo J Costa^{1

3}, Miguel Machuqueiro^{1

3}

Affiliations

¹ BioISI - Instituto de Biossistemas e Ciências Integrativas, Faculdade de Ciências, Universidade de Lisboa, Lisboa, 1749-016, Portugal.
² Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
³ Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal.

Abstract

Several factors affect the passive membrane permeation of small molecules, including size, charge, pH, or the presence of specific chemical groups. Understanding these features is paramount to identifying or designing drug candidates with optimal ADMET properties and this can be achieved through experimental/knowledge-based methodologies or using computational approaches. Empirical methods often lack detailed information about the underlying molecular mechanism. In contrast, Molecular Dynamics-based approaches are a powerful strategy, providing an atomistic description of this process. This technique is continuously growing, featuring new related methodologies. In this work, the recent advances in this research area will be discussed.

Keywords: 0000; 1111; Constant-pH MD; Enhanced sampling; Lipid bilayer; Lipophilicity; Passive diffusion.