Computer Simulation of Small Molecule Permeation Across a Lipid Bilayer: Dependence on Bilayer Properties and Solute Volume, Size, and Cross-sectional Area

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2004 Jul 9

PMID 15240439

Citations 44

Authors

D Bemporad

C Luttmann

J W Essex

Affiliations

Soon will be listed here.

Abstract

Cell membrane permeation is required for most drugs to reach their biological target, and understanding this process is therefore crucial for rational drug design. Recent molecular dynamics simulations have studied the permeation of eight small molecules through a phospholipid bilayer. Unlike experiments, atomistic simulations allow the direct calculation of diffusion and partition coefficients of solutes at different depths inside a lipid membrane. Further analyses of the simulations suggest that solute diffusion is less size-dependent and solute partitioning more size-dependent than was commonly thought.

Citing Articles

Improving the antimicrobial activity of RP9 peptide through theoretical and experimental investigation.

Anahid M, Mahnam K, Saffar B Biochem Biophys Rep. 2025; 41:101953.

PMID: 40034258 PMC: 11872504. DOI: 10.1016/j.bbrep.2025.101953.

Assessing the Interaction between Dodecylphosphocholine and Dodecylmaltoside Mixed Micelles as Drug Carriers with Lipid Membrane: A Coarse-Grained Molecular Dynamics Simulation.

Gholizadeh A, Amjad-Iranagh S, Halladj R ACS Omega. 2024; 9(39):40433-40445.

PMID: 39372004 PMC: 11447843. DOI: 10.1021/acsomega.4c02551.

Examine stability polyvinyl alcohol-stabilized nanosuspensions to overcome the challenge of poor drug solubility utilizing molecular dynamic simulation.

Abdollahi S, Raissi H, Farzad F Sci Rep. 2024; 14(1):17386.

PMID: 39075104 PMC: 11286956. DOI: 10.1038/s41598-024-68362-2.

New understanding of multidrug efflux and permeation in antibiotic resistance, persistence, and heteroresistance.

Manrique P, Lopez C, Gnanakaran S, Rybenkov V, Zgurskaya H Ann N Y Acad Sci. 2022; 1519(1):46-62.

PMID: 36344198 PMC: 9839546. DOI: 10.1111/nyas.14921.

PE and PET oligomers' interplay with membrane bilayers.

Jarvenpaa J, Perkkio M, Laitinen R, Lahtela-Kakkonen M Sci Rep. 2022; 12(1):2234.

PMID: 35140293 PMC: 8828856. DOI: 10.1038/s41598-022-06217-4.

References

Brunner J, Graham D, Hauser H, Semenza G . Ion and sugar permeabilities of lecithin bilayers: comparison of curved and planar bilayers. J Membr Biol. 1980; 57(2):133-41. DOI: 10.1007/BF01868999. View

Todd A, Mehlhorn R, MACEY R . Amine and carboxylate spin probe permeability in red cells. J Membr Biol. 1989; 109(1):41-52. DOI: 10.1007/BF01870789. View

Xiang T, Chen J, Anderson B . A quantitative model for the dependence of solute permeability on peptide and cholesterol content in biomembranes. J Membr Biol. 2000; 177(2):137-48. DOI: 10.1007/s002320001107. View

Pratt L, Pohorille A . Hydrophobic effects and modeling of biophysical aqueous solution interfaces. Chem Rev. 2002; 102(8):2671-92. DOI: 10.1021/cr000692+. View

Cohen B . The permeability of liposomes to nonelectrolytes. I. Activation energies for permeation. J Membr Biol. 1975; 20(3-4):205-34. DOI: 10.1007/BF01870637. View

Xiang T, Chen X, Anderson B . Transport methods for probing the barrier domain of lipid bilayer membranes. Biophys J. 1992; 63(1):78-88. PMC: 1262126. DOI: 10.1016/S0006-3495(92)81581-3. View

Seelig J . Deuterium magnetic resonance: theory and application to lipid membranes. Q Rev Biophys. 1977; 10(3):353-418. DOI: 10.1017/s0033583500002948. View

Bean R, Shepherd W, Chan H . Permeability of lipid bilayer membranes to organic solutes. J Gen Physiol. 1968; 52(3):495-508. PMC: 2225820. DOI: 10.1085/jgp.52.3.495. View

Tu K, Tarek M, Klein M, Scharf D . Effects of anesthetics on the structure of a phospholipid bilayer: molecular dynamics investigation of halothane in the hydrated liquid crystal phase of dipalmitoylphosphatidylcholine. Biophys J. 1998; 75(5):2123-34. PMC: 1299885. DOI: 10.1016/S0006-3495(98)77655-6. View

10.

Walter A, Gutknecht J . Monocarboxylic acid permeation through lipid bilayer membranes. J Membr Biol. 1984; 77(3):255-64. DOI: 10.1007/BF01870573. View

11.

Venable R, Zhang Y, Hardy B, Pastor R . Molecular dynamics simulations of a lipid bilayer and of hexadecane: an investigation of membrane fluidity. Science. 1993; 262(5131):223-6. DOI: 10.1126/science.8211140. View

12.

Alper H, Stouch T . Solute diffusion in lipid bilayer membranes: an atomic level study by molecular dynamics simulation. Biochemistry. 1993; 32(47):12624-37. DOI: 10.1021/bi00210a010. View

13.

Smith R, Porter E, Miller K . The solubility of anesthetic gases in lipid bilayers. Biochim Biophys Acta. 1981; 645(2):327-38. DOI: 10.1016/0005-2736(81)90204-2. View

14.

Xiang T, Anderson B . Permeability of acetic acid across gel and liquid-crystalline lipid bilayers conforms to free-surface-area theory. Biophys J. 1997; 72(1):223-37. PMC: 1184311. DOI: 10.1016/S0006-3495(97)78661-2. View

15.

Nagle J, Tristram-Nagle S . Structure of lipid bilayers. Biochim Biophys Acta. 2000; 1469(3):159-95. PMC: 2747654. DOI: 10.1016/s0304-4157(00)00016-2. View

16.

Katz Y, Diamond J . Thermodynamic constants for nonelectrolyte partition between dimyristoyl lecithin and water. J Membr Biol. 1974; 17(2):101-20. DOI: 10.1007/BF01870175. View

17.

Dix J, Kivelson D, Diamond J . Molecular motion of small nonelectrolyte molecules in lecithin bilayers. J Membr Biol. 1978; 40(4):315-42. DOI: 10.1007/BF01874162. View

18.

Walter A, Gutknecht J . Permeability of small nonelectrolytes through lipid bilayer membranes. J Membr Biol. 1986; 90(3):207-17. DOI: 10.1007/BF01870127. View

19.

Diamond J, Katz Y . Interpretation of nonelectrolyte partition coefficients between dimyristoyl lecithin and water. J Membr Biol. 1974; 17(2):121-54. DOI: 10.1007/BF01870176. View

20.

Bochain A, Estey L, Haronian G, Reale M, Rojas C, Cramer J . Determination of catecholamine permeability coefficients for passive diffusion across phospholipid vesicle membranes. J Membr Biol. 1981; 60(1):73-6. DOI: 10.1007/BF01870834. View