Anisotropic Solvent Model of the Lipid Bilayer. 2. Energetics of Insertion of Small Molecules, Peptides, and Proteins in Membranes

• Published in: Journal of chemical information and modeling Vol. 51; no. 4; pp. 930 - 946
• Main Authors: Lomize, Andrei L, Pogozheva, Irina D, Mosberg, Henry I
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 25-04-2011
• Subjects: Adsorption and desorption kinetics; evaporation and condensation; Algorithms; Anisotropy; Biological and medical sciences; Biological membranes; Cell Membrane - chemistry; Chemical bonds; Computational Biochemistry; Computer Simulation; Condensed matter: structure, mechanical and thermal properties; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Hydrogen Bonding; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Lipids; Lipids - chemistry; Membrane physicochemistry; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membranes; Models, Molecular; Molecular biophysics; Molecules; Peptides - chemistry; Peptides - metabolism; Physics; Protein Conformation; Proteins; Solid-fluid interfaces; Solvents; Solvents - chemistry; Surfaces and interfaces; thin films and whiskers (structure and nonelectronic properties); Thermodynamics; Water - chemistry; Energetics; Energy method; Membrane protein; Peptides; Insertion; Experimental study; Modeling; Lipid bilayers; Solvation; Aqueous medium; Proteomics; Database; Polarity; Alkalinity; Large scale; Solvent; Energy transfer
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/ci200020k

A new computational approach to calculating binding energies and spatial positions of small molecules, peptides, and proteins in the lipid bilayer has been developed. The method combines an anisotropic solvent representation of the lipid bilayer and universal solvation model, which predicts transfer energies of molecules from water to an arbitrary medium with defined polarity properties. The universal solvation model accounts for hydrophobic, van der Waals, hydrogen-bonding, and electrostatic solute−solvent interactions. The lipid bilayer is represented as a fluid anisotropic environment described by profiles of dielectric constant (ε), solvatochromic dipolarity parameter (π*), and hydrogen bonding acidity and basicity parameters (α and β). The polarity profiles were calculated using published distributions of quasi-molecular segments of lipids determined by neutron and X-ray scattering for DOPC bilayer and spin-labeling data that define concentration of water in the lipid acyl chain region. The model also accounts for the preferential solvation of charges and polar groups by water and includes the effect of the hydrophobic mismatch for transmembrane proteins. The method was tested on calculations of binding energies and preferential positions in membranes for small-molecules, peptides and peripheral membrane proteins that have been experimentally studied. The new theoretical approach was implemented in a new version (2.0) of our PPM program and applied for the large-scale calculations of spatial positions in membranes of more than 1000 peripheral and integral proteins. The results of calculations are deposited in the updated OPM database (http://opm.phar.umich.edu).