The fast method for quantitative estimation of distribution of hydrophobicand hydrophilic segments in alpha-helices of membrane proteins

The work presents a fast quantitative approach for estimating orientations of hydrophilic and hydrophobic regions in the helical wheels of membrane pr oteins. The common hydropathy analysis provides the estimate of the integra l hydrophobicity in a moving window that scans amino acid sequence. The new parameter, orientation hydrophobicity, is based on the estimate of hydroph obicity of the angular segment that scans the helical wheel of a given amin o acid sequence. The corresponding procedure involves the treatment of tran smembrane helices as cylinders with equal surface elements for each amino a cid residue. The oriented hydrophobicity, P (phi), phi = 0 degrees-360 degr ees, of the helical cylinder is given as a sum of hydrophobicities of indiv idual amino acids that are taken as the S-functions of the angle between th e center of amino acid acid surface element and the center of the segment. Non-zero contribution to P (phi) come only from the amino acids belonging t o the angular segment for the given angle phi. The size of the angular segm ent is related to the size of the channel pore. The amplitudes of amino aci d S-functions are calibrated in the way that their maximum values (reached when the amino acid is completely exposed into the pore) equal the correspo nding hydropathy index in the selected scale (here taken as Goldman Engelma n - Steitz hydropathy scale). The given procedure is applied in the studies of three ion channels with a well characterized three-dimensional structures where the channel pore is f ormed by a bundle of alpha-helices: cholera toxin B, nicotinic acetylcholin e homopentameric alpha 7 receptor, and phospholamban. The estimated maximum of hydrophilic properties at the helical wheels are in a good agreement wi th the apatial orientations of alpha-helices in the corresponding channel p ores.