Overbinding of ions is a common and well-known problem in classical molecular dynamics simulations. One of its main causes is the absence of electronic polarizability in the force fields. The current approaches for minimizing overbinding typically either retain the original charges and use an ad hoc readjustment of the Lennard-Jones parameters as done in the nonbonded fix (NBFIX) approach or rescale the charges using a theoretical framework. The goal in the latter is to include shielding produced by the missing electronic polarizability as done in the electronic continuum correction (ECC) approach. NBFIX and ECC are the most common corrections, and we compare their performance to the default parameterizations provided by five different commonly used biomolecular force fields, OPLS-AA/L, CHARMM27, CHARMM36m, CHARMM22*, and AMBER99SB-ILDN. As test systems, we use poly-α,l-glutamic and poly-α,l-aspartic amino acid molecules in explicit water together with Na+ and K+ counterions. We demonstrate that the different force fields yield results that are not only quantitatively but also qualitatively different. The resulting structures of the macroions depend strongly on the model for ions. NBFIX corrections alleviate the problem of overbinding, resulting in extended peptides. The ECC corrections depend nontrivially on the original underlying model, and despite being based on a theoretical framework, they cannot always solve the problem.

Institute of Macromolecular Compounds Russian Academy of Sciences Bolshoy pr 31 St Petersburg 199004 Russia

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo náměstí 542 2 Prague 6 CZ166 10 Czech Republic

References provided by Crossref.org

NMR-Derived Salt Bridges in Insulin Analogue: Resolving Artifactual Overbinding in Molecular Dynamics via Charge Scaling

Developing and Benchmarking Sulfate and Sulfamate Force Field Parameters via Ab Initio Molecular Dynamics Simulations To Accurately Model Glycosaminoglycan Electrostatic Interactions

Effective Inclusion of Electronic Polarization Improves the Description of Electrostatic Interactions: The prosECCo75 Biomolecular Force Field

Curvature Matters: Modeling Calcium Binding to Neutral and Anionic Phospholipid Bilayers

Influence of electronic polarization on the binding of anions to a chloride-pumping rhodopsin

Changes in the Local Conformational States Caused by Simple Na+ and K+ Ions in Polyelectrolyte Simulations: Comparison of Seven Force Fields with and without NBFIX and ECC Corrections