Dielectric-dependent strength of interlipid H-bonding in biomembranes: a model case study.

Journal of Chemical Information and Modeling. 2019. Vol. 59. No. 6. P. 2765–2775.

Efremov R.

Atomistic aspects of the structural organization, dynamics, and functioning of hydrated lipid bilayers - model cell membranes - are primarily governed by the fine balance of intermolecular interactions between all constituents of these systems. Besides the hydrophobic effect, which shapes the overall skeleton of lipid membranes, very important contribution to their behavior is made by hydrogen bonds (H-bonds) between lipid head groups. The latter determine such crucial phenomena in cell membranes, like dynamic ultra-nanodomain organization, hydration, fine-tuning of microscopic physico-chemical properties that allow the membrane to adapt quickly when binding/insertion external agents (proteins, etc.) The characteristics of such H-bonds (strength, spatial localization, etc.) dramatically depend on the local polarity properties of the lipid-water environment. In this work, we calculated free energies of H-bonded complexes between typical donor (NH3+, NH, OH) and acceptor (C=O, OH, COO-, COOH) groups of lipids in vacuo and in a set of explicit solvents with dielectric constants (ε) from 1 to 78.3, which mimic membrane environment at different depth. This was done using Monte Carlo simulations and an assessment of the corresponding Potential of Mean Force profiles. The strongest H-bonded complexes were observed in the nonpolar environment and their strength increased sharply with decreasing ε below 17. When ε changed, the largest free energy gain (> 10.8 kcal/mol) was observed for pairs of acceptors C=O and O(H) with donor NH3+. The complexation of the same acceptors with NH-donor in this range of ε was rather less sensitive to the environmental polarity: by ~1.5 kcal/mol. Dielectric-dependent interactions of polar lipid groups with water were evaluated as well. The results explain the delicate balance that determines the unique pattern of H-bonds for a particular lipid bilayer. Understanding the factors that regulate the propensity to H-bonding in lipid bilayers provides a fundamental basis for the rational design of new membrane nano-objects with predefined properties.

Keywords: метод Монте-Карло, Monte Carlo method, molecular modeling, диэлектрическая проницаемость, free energy of intermolecular interactions, свободная энергия межмолекулярных взаимодействий, компьютерное молекулярное моделирование, hydrogen bonds, водородные связи, biomembranes, dielectric permeability, биологические мембраны

Publication based on the results of: Supercomputer technologies of atomic modeling in the material science and physics of biomembranes (2019)