Protonation of DMPC in a Bilayer Environment Using a Linear Response Approximation

• Published in: Journal of chemical theory and computation Vol. 10; no. 5; pp. 2176 - 2184
• Main Authors: Teixeira, Vitor H, Vila-Viçosa, Diogo, Baptista, António M, Machuqueiro, Miguel
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 13.05.2014
• ISSN: 1549-9618; 1549-9626; 1549-9626
• DOI: 10.1021/ct5000082

pH is a very important property, influencing all important biomolecules such as proteins, nucleic acids, and lipids. The effect of pH on proteins has been the subject of many computational works in recent years. However, the same has not been done for lipids, especially in their most biologically relevant environment: the bilayer. A reason for this is the inherent technical difficulty in dealing with this type of periodic systems. Here, we tackle this problem by developing a Poisson–Boltzmann-based method that takes in consideration the periodic boundary conditions of lipid bilayer patches. We used this approach with a linear response approximation to calculate the pK a value of a DMPC molecule when diluted in zwitterionic lipids. Our results show that DMPC protonation only becomes relevant at quite low pH values (2–3). However, when it happens, it has a strong impact on lipid conformations, leading to significant heterogeneity in the membrane.