Computation of the permanent dipole moment of α-chymotrypsin from linear-scaling semiempirical quantum mechanical methods

The permanent dipole moment of α-chymotrypsin (α-CT) has been computed by means of linear-scaling semiempirical (AM1, PM3 and PM5) quantum mechanical methods. Solvent effects were accounted for implicitly by means of the conductor-like screening model (COSMO). The dipole moment computed at pH 7. 0 with the PM5/COSMO (ε = 80) method corresponds to 492 D. This theoretical value compares well with experiments performed with the electric dichroism technique, provided that the asymptotic behavior of the measured macrodipole in the 4.2-8.3 pH range is taken into account. Explicit solvent models were also investigated. However, the magnitude of the calculated dipole turns out to depend upon the number of discrete water molecules added to the protein. Finally, the computed net (Mulliken) charge on each side-chain residue of α-CT indicates that Asp102 is the most polarized residue among those of the catalytic triad. Possible implications of the macrodipole of α-CT for enzymatic catalysis are also discussed.