title: Interaction of charged amino-acid side chains with ions: an optimization strategy for classical force fields.
abstract: Many well-established classical biomolecular force fields, fitted on the solvation properties of single ions, do not necessarily describe all the details of ion pairing accurately, especially for complex polyatomic ions. Depending on the target application, it might not be sufficient to reproduce the thermodynamics of ion pairing, but it may also be necessary to correctly capture structural details, such as the coordination mode. In this work, we analyzed how classical force fields can be optimized to yield a realistic description of these different aspects of ion pairing. Given the prominent role of the interactions of negatively charged amino-acid side chains and divalent cations in many biomolecular systems, we chose calcium acetate as a benchmark system to devise a general optimization strategy that we applied to two popular force fields, namely, GROMOS and OPLS-AA. Using experimental association constants and first-principles molecular dynamics simulations as a reference, we found that small modifications of the van der Waals ion-ion interaction parameters allow a systematic improvement of the essential thermodynamic and structural properties of ion pairing.
authors.affiliation: Max Planck Institute for Polymer Research , Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Kahlen
authors.forename: Leila
authors.initials: L
authors.lastname: Salimi
authors.forename: Marialore
authors.initials: M
authors.lastname: Sulpizi
authors.forename: Christine
authors.initials: C
authors.lastname: Peter
authors.forename: Davide
authors.initials: D
authors.lastname: Donadio
mesh_terms: D000085:Acetates / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D017610:Calcium Compounds / Q000737:chemistry; D006860:Hydrogen Bonding; D007477:Ions / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D055672:Static Electricity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D000085:Acetates; D000596:Amino Acids; D017610:Calcium Compounds; D007477:Ions; D014867:Water; C120662:calcium acetate