Multi-layer coarse-graining polarization model for treating electrostatic interactions of solvated α-conotoxin peptides

摘要

A multi-layer coarse-graining (CG) model is presented for treating the electrostatic interactions of solvated α-conotoxin peptides. According to the sensitivity to the electrostatic environment, a hybrid set of electrostatic parameters, such as secondary-structure- and residue-based dipoles, and atom-centered partial charges, are adopted. For the polarization inert secondary-structures and residues, the fragment dipole moments are distributed within narrow ranges with the magnitude close to zero. The coarse-graining fragment dipoles are parameterized from a large training set (10 000 configurations) to reproduce the electrostatic features of molecular fragments. In contrast, the electrostatically sensitive atoms exhibit large fluctuations of charges with the varied environments. The environment-dependent variable charges are updated in each energetic calculation. The electrostatic interaction of the whole chemical system is hence partitioned into several sub-terms coming from the fragment dipole-dipole, (fragment) dipole-(atom) charge, and atom charge-charge interactions. A large number of test calculations on the relative energies of cyclo-peptide conformers have demonstrated that the multi-layer CG electrostatic model presents better performance than the non-polarized force fields, in comparison with the density-functional theory and the fully polarized force field model. The selection of CG fragment centers, mass or geometric center, has little influence on the fragment-based dipole-dipole interactions. The multi-layer partition of electrostatic polarization is expected to be applied to many biologically interesting and complicated phenomena.