Permeability of drugs and hormones through a lipid bilayer: insights from dual-resolution molecular dynamics

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

“…15,[18][19][20][21] In contrast, most studies of larger molecules that are at least the size of the amino acids studied in this work show relatively flat diffusion profiles in homogenous lipid bilayers. 25,27,30 Thus, our translational diffusion results are consistent with other reported values for larger molecules.…”

“…Although a direct comparison does not exist for phenylalanine and tyrosine, our results are roughly the same order of magnitude as those obtained using the same model for small molecules. 25 Previous studies of tryptophan using the more advanced method of milestoning report permeation times on the time scale of hours, which are also in agreement with experimental results. 43,44,85,86 Most other studies have also reported much larger and faster permeability coefficients using the inhomogeneous solubilitydiffusion model, which has been discussed in great detail in other works.…”

“…14 Recent molecular dynamics studies have focused on a wide variety of molecules passively diffusing through membranes, such as water, [15][16][17] small molecules, [18][19][20][21][22][23] model drug compounds, 6,22,24,25 analgesics, [26][27][28] drug delivery systems, 29,30 dyes, 31,32 other lipids, 33,34 nanoparticles, [35][36][37] toxins, 38 small peptides, 39,40 and even transmembrane proteins. 41,42 However, only a handful of MD studies have examined amino acid-related systems and are confined to tryptophan, [43][44][45] arginine, 46,47 lysine, 47 and amino acid analogues.…”

Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

“…There are several molecular features that govern the behavior of a drug in cell membranes such as size, shape, solubility, hydrophilicity, lipophilicity, and pK a , among others. Previously, many authors have reported studies of the interaction of drugs and membrane models with experimental technics (Nunes et al 2011;Lucio et al 2009;Fuchs et al 1990) and molecular dynamic (MD) simulations (Robinson et al 1995;Gabdouline et al 1996;Smondyrev andBerkowitz 1999, 2001;Hofsäß et al 2003;Pereira et al 2004;Falck et al 2006;Högberg et al 2007;Seddon et al 2009;Sirk et al 2009;Boggara and Krishnamoorti 2010;Witzke et al 2010;Orsi andEssex 2010, Koukoulitsa et al 2011;Nitschke et al 2012;Poger and Mark 2013;Loverde 2014;Jalili and Saeedi 2016). In particular, studies based on drug partitioning in lipid bilayers and the thermodynamics of drug/lipid interaction have great importance in understanding the reaction mechanisms of antitumor drugs and to design new cell membrane-targeted drugs (Boggara and Krishnamoorti 2010;Jendrossek and Handrick 2003;Goldstein et al 2011;Choi et al 2013).…”

“…For these kinds of molecules, it is important to identify their interaction with the molecules that compose the membranes and try to understand the roles of the hydrophilic and lipophilic groups. In this direction, the MD simulations are an useful tool and can identify the location of the drug in the membrane models (Boggara and Krishnamoorti 2010;Loverde 2014;Högberg et al 2007;Orsi and Essex 2010). It has been adopted in theoretical studies of biological membrane models (Tieleman et al 1997;Mark 2010, 2012) and partitioning and interaction of drugs in lipid bilayers (Fuchs et al 1990;Omote and Al-Shawi 2006;MacCallum and Tieleman 2006;Bemporad et al 2004).…”