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Molecular hydrophobicity potential (MHP) approach

MHP, also referred to as MLP (molecular lipophilic potential), is an empirical approach for evaluation and detailed visualization of the hydrophobic / hydrophilic properties of organic molecules or macromolecules.

The formalism of MHP is based on empirical atomic hydrophobicity constants (i.e. „hydrophobicity charges“) derived form partition coefficients logP of various compounds between polar and apolar media, usually water / n-octanol [Furet et al., 1988; Ghose et al., 1998].

Like the electrostatic Coulomb potential, MHP is supposed to have some distance-dependence. However, no universal equation has been proposed for this, the most common way being use an exponential [Fauchère et al., 1988; Gaillard et al., 1994] or a smoothed step-function, also referred to as the Fermi-like potential [Heiden, Moeckel & Brickmann, 1993].

Fig. 1. MHP distribution on molecular surface allows detailed visualization of its hydrophobic / hydrophilic properties. The sum in the equation is taken over all atoms of the molecule.

MHP formalism is a helpful technique in numerous areas of molecular modeling. See a review on using molecular lipophilicity in protein modeling and drug design for more information [Efremov et al., 2007].

Ligand-protein docking and scoring. Upon complex formation hydrophobic parts of a ligand molecule tend to avoid contacts with polar medium by burying themselves into hydrophobic pockets of the active site. This effect, observed in numerous ligand-protein complexes, has been shown to improve the docking results in particular cases when included as an additional term into the scoring function [Pyrkov et al., 2007].

Membrane-spanning α-helices. Previously, we have developed a MHP-based molecular modeling approach to analyze the spatial polarity properties of membrane-bound peptides and to calculate the interlocation of membrane-spanning helical hairpins [Efremov et al., 1992ab; Efremov & Vergoten, 1995]. This procedure provides a pictorial 2D-representation of nonpolar and polar patterns on the helix surfaces. Such representations have been proved to be very helpful in further analysis of protein-protein interactions in membrane [Vereschaga et al., 2005; Efremov et al., 2006].

Peripheral membrane peptides and proteins. The 2D hydrophobicity map has also been successfully used in investigations of functional mechanisms of peripheral membrane antimicrobial peptides and rational peptide design [Volynsky et al., 2005; Polyansky et al., 2006].

Fig. 2. Spatial hydrophobic properties of the transmembrane helix TM2 (P71-H100) in bovine visual rhodopsin. A. Two-dimensional isopotential map of the molecular hydrophobicity potential on the peptide surface. The value on the X axis corresponds to the rotation angle about the helix axis; the parameter on the Y axis is the distance along the helix axis. The positions of residues are indicated by letters. Membrane-exposed residues in the X-ray structure of rhodopsin are underlined. B. The scheme illustrating a coordinate system (α, :Z) used for presentation of MHP-properties of the peptide. The peptide backbone, side chains, and surface are indicated with sticks, ribbon, and semi-transparent Connolly surface, respectively.

Read about analysis of hydrophobic organization of proteins.

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