Indole localization in lipid membranes revealed by molecular simulation

Area of Science:

• Biophysics
• Computational Chemistry
• Membrane Biology

Background:

• Tryptophan and indole analogs associate with lipid bilayer interfaces.
• Phenylalanine and benzene analogs distribute throughout lipid bilayers without specific interfacial localization.

Purpose of the Study:

• To investigate the detailed localization and orientation of indole and benzene within a POPC lipid bilayer using molecular dynamics.
• To identify the key factors governing the differential partitioning and binding of indole and benzene in lipid bilayers.

Main Methods:

• Molecular dynamics simulations of indole and benzene within a 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) bilayer.
• Analysis of molecular interactions, including hydrogen bonding, cation-pi interactions, and electrostatic effects, using various partial charge sets.

Main Results:

• Indole localizes at three sites: near glycerol, near choline, and in the hydrocarbon core.
• Benzene also occupies these sites, with the hydrocarbon core being the most stable.
• Indole's transfer to the core is hydrophobic, while interfacial binding is enthalpy-driven.
• Electrostatic interactions, including hydrogen bonding and dipole-field interactions, significantly influence localization.

Conclusions:

• Indole and benzene exhibit distinct binding preferences within lipid bilayers due to a combination of hydrophobic and electrostatic factors.
• Interfacial localization of indole is primarily enthalpy-driven, suggesting specific interactions with lipid headgroups.
• Molecular dynamics simulations provide insights into the complex interplay of forces governing small molecule partitioning in biological membranes.