Abstract
<jats:p>Polarizable force fields such as AMOEBA provide a physically richer description of molecular interactions than fixed-charge models through permanent multipoles and explicit polarization with induced dipoles. However, the intramolecular treatment of covalently connected atom pairs remains complicated by topology-dependent scaling rules applied separately to different nonbonded components. In particular, the distinct treatments in the electric-field and energy calculations in AMOEBA’s polarization scheme complicate parameterization and model implementation and introduce extra computational overhead. In this work, we extend our recently developed bonded-coupling framework for short-range intramolecular interactions to the AMOEBA polarizable force field. The complex AMOEBA intramolecular scaling scheme is replaced by a unified scaling protocol, while 1–2, 1–3, and 1–4 interactions are described entirely by bonded and bonded-coupling terms without any short-range nonbonded contribution. We apply this framework to reparametrize the protein backbone and demonstrate its improved ability to reproduce quantum-mechanical potential energy surfaces and yield reasonable results in condensed-phase simulations.</jats:p>