Molecular simulations can elucidate atomistic-level mechanisms of key biological processes, which are often hardly accessible to experiment. However, the results of the simulations can only be as trustworthy as the underlying simulation model. In many of these processes, interactions between charged moieties play a critical role. Current empirical force fields tend to overestimate such interactions, often in a dramatic way, when polyvalent ions are involved. The source of this shortcoming is the missing electronic polarization in these models. Given the importance of such biomolecular systems, there is great interest in fixing this deficiency in a computationally inexpensive way without employing explicitly polarizable force fields. Here, we review the electronic continuum correction approach, which accounts for electronic polarization in a mean-field way, focusing on its charge scaling variant. We show that by pragmatically scaling only the charged molecular groups, we qualitatively improve the charge-charge interactions without extra computational costs and benefit from decades of force field development on biomolecular force fields.

CNRS Université de Paris UPR 9080 Laboratoire de Biochimie Théorique 13 rue Pierre et Marie Curie 75005 Paris France

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo nam 2 Prague 6 166 10 Czech Republic

References provided by Crossref.org

Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery

Molecular dynamics simulations unveil the aggregation patterns and salting out of polyarginines at zwitterionic POPC bilayers in solutions of various ionic strengths

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

Can calmodulin bind to lipids of the cytosolic leaflet of plasma membranes?

Building Water Models Compatible with Charge Scaling Molecular Dynamics

Hydration of biologically relevant tetramethylammonium cation by neutron scattering and molecular dynamics

Nonaqueous Ion Pairing Exemplifies the Case for Including Electronic Polarization in Molecular Dynamics Simulations

Efficient Simulations of Solvent Asymmetry Across Lipid Membranes Using Flat-Bottom Restraints

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

Ionic Strength and Solution Composition Dictate the Adsorption of Cell-Penetrating Peptides onto Phosphatidylcholine Membranes

Accurate Simulations of Lipid Monolayers Require a Water Model with Correct Surface Tension

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