Protein Macrodipoles

The macrodipole of a protein is a physical quantity which provides useful information about the imbalance (or polarization) of electronic charge of the molecule. Simply put, the protein macrodipole (PM) arises from the spatial arrangement of both charged amino acid groups and the peptide bond dipoles of the protein. It should be kept in mind, however, that all the electrons and nuclei of the protein contribute to built up the macrodipole. The calculation of the PM is accomplished through an electronic structure calculation first by computing the electronic wavefunction, then the dipole integrals over the basis functions, and finally the dipole moment. The Debye is a non-SI unit used to express the magnitude of a dipole moment. A small polar molecules such as water possesses a dipole moment of 3.5 D. Proteins are characterized by dipole moments ranging from one hundred Debyes up to several thousand Debyes. For example, the experimentally-determined dipole moment of alpha-chymotrypsin has a magnitude of ~500 D at pH 7 (Antosiewicz & Porschke, Biochemistry, 1989). The computed dipoles shown below have a magnitude of 492 D (in continuum water) and 371 D (water droplet). Further details can be found in my first paper on QM-based PMs: Computation of the permanent dipole moment of alpha-chymotrypsin from linear-scaling semiempirical quantum mechanical methods, JOURNAL OF MOLECULAR STRUCTURE (THEOCHEM) 664-665 (2003) 197-205.

Below are shown the computed macrodipoles of full-length KcsA potassium channel and ClC chloride channel. The former has a magnitude of 403 D and is aligned along the fourfold axis of the homotetramer while the latter has a magnitude of 1983 D and is aligned along the twofold axis of the homodimer. For further details see my recent paper: Macrodipoles of Potassium and Chloride Ion Channels as Revealed by Electronic Structure Calculations, JOURNAL OF MOLECULAR STRUCTURE (THEOCHEM) 950 (2010) 79-82.