Generalized Born Model with a Simple, Robust Molecular Volume Correction

Abstract

Generalized Born (GB) models provide a computationally efficient means of representing the electrostatic effects of solvent and are widely used, especially in molecular dynamics (MD). A class of particularly fast GB models is based on integration over an interior volume approximated as a pairwise union of atom spheres-effectively, the interior is defined by a van der Waals rather than Lee-Richards molecular surface. The approximation is computationally efficient, but if uncorrected, allows for high dielectric (water) regions smaller than a water molecule between atoms, leading to decreased accuracy. Here, an earlier pairwise GB model is extended by a simple analytic correction term that largely alleviates the problem by correctly describing the solvent-excluded volume of each pair of atoms. The correction term introduces a free energy barrier to the separation of non-bonded atoms. This free energy barrier is seen in explicit solvent and Lee-Richards molecular surface implicit solvent calculations, but has been absent from earlier pairwise GB models. When used in MD, the correction term yields protein hydrogen bond length distributions and polypeptide conformational ensembles that are in better agreement with explicit solvent results than earlier pairwise models. The robustness and simplicity of the correction preserves the efficiency of the pairwise GB models while making them a better approximation to reality.

Effect of the solvent on the conformational behavior of the alanine dipeptide deduced from MD simulations

“…In this case the cutoff for the non-bonded interactions was increased to 12 Å to assure the inclusion of the maximum interatomic distance when the alanine dipeptide is in its extended conformation. GB calculations were carried out by means of the neck GB model that adds a geometrically based molecular volume correction term accounting for interstitial high dielectrics to pairwise GB models [39].…”

Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly

“…All simulations were carried out using the AMBER v12 Molecular Dynamics package with the f99SB force field improved with NMR observables (ff99SBnmr) (46)(47)(48). The Generalized Born implicit solvent approach was adopted using specifically the gb7 model as this is ∼100-fold faster compared with explicit solvent simulations when graphical processor units are used (49)(50)(51). Production gb7 simulations were carried out for 1,000 ns using 1 fs as the time step.…”

Electrostatic interactions in biological DNA-related systems

“…Arg was claimed to be preferred over Lys in the minor grooves because of a lower self-energy cost to remove a larger guanidinium group of Arg + from its hydrated state in solution and bring it in contact to the DNA, than to do the same for a smaller ammonium group of the Lys + residue. 263 The reason is the Born ES self-energy that scales inversely proportional to the ''ion'' radius [264][265][266][267][268] (see also recent numerical studies on the hydration of small organic molecules 269,270 and polypeptides [271][272][273] ). Being valid for large structural complexes, the ES complementarity recognition model however fails for small DNAprotein complexes, with simple standard motifs of DNA recognition (e.g., helix-turn-helix, zinc finger, and leucine zipper).…”