Treating hydrogen bonding in ab initio calculation of biopolymers

We present a general scheme to treat backbone hydrogen bonding in protein using the molecular fractionation with conjugate caps (MFCC) approach. In this approach, molecular caps are employed to mimic the hydrogen bonding environment of protein fragments that are calculated individually. Using this scheme in the MFCC method, we carried out explicit numerical calculations for a number of secondary structures of proteins, including the α-helix and β-sheet. The calculated electron densities, electrostatic potentials, and dipole moment are compared with those from the standard full system ab initio calculations. The result shows that the current treatment using the hydrogen bond cap gives an accurate description of the hydrogen bonding effect and accurate dipole moment. In contrast, calculation using the standard force field (FF) approach gives dipole moments that are in huge error (i.e., significantly smaller) than the quantum result for helix structures due to the lack of polarization effect with fixed partial charges. The present study demonstrates that the MFCC approach can quantitatively describe hydrogen bonding in practical ab initio calculation of proteins. Our result also underscores the importance of the polarization effect in backbone hydrogen bonding of protein. This could have significant implication in studying the electrostatic interaction of proteins, such as protein solvation.