Generalized born model with a simple smoothing function

Abstract

Based on recent developments in generalized Born (GB) theory that employ rapid volume integration schemes (M. S. Lee, F. R. Salabury, Jr., and C. L. Brooks III, J Chem Phys 2002, 116, 10606) we have recast the calculation of the self-electrostatic solvation energy to utilize a simple smoothing function at the dielectric boundary. The present GB model is formulated in this manner to provide consistency with the Poisson-Boltzmann (PB) theory previously developed to yield numerically stable electrostatic solvation forces based on finite-difference methods (W. Im, D. Beglov, and B. Roux, Comp Phys Commun 1998, 111, 59). Our comparisons show that the present GB model is indeed an efficient and accurate approach to reproduce corresponding PB solvation energies and forces. With only two adjustable parameters--a(0) to modulate the Coulomb field term, and a(1) to include a correction term beyond Coulomb field--the PB solvation energies are reproduced within 1% error on average for a variety of proteins. Detailed analysis shows that the PB energy can be reproduced within 2% absolute error with a confidence of about 95%. In addition, the solvent-exposed surface area of a biomolecule, as commonly used in calculations of the nonpolar solvation energy, can be calculated accurately and efficiently using the simple smoothing function and the volume integration method. Our implicit solvent GB calculations are about 4.5 times slower than the corresponding vacuum calculations. Using the simple smoothing function makes the present GB model roughly three times faster than GB models, which attempt to mimic the Lee-Richards molecular volume.

On the Mechanism Underlying (23S)-25-Dehydro-1α(OH)-vitamin D3-26,23-lactone Antagonism of hVDRwt Gene Activation and Its Switch to a Superagonist

“…The flexible docking protocol variables changed from the default parameters were as follows: a 10.0-Å docking sphere was defined by searching the apo-VDR molecule for putative binding sites; the number of flexible docking residues allowed for structural refinement was set to 12; the top 5 hits were saved for each protein-ligand pair, and a simulated annealing step was performed. The Generalized Born with Molecular Volume method (23,24) was used to determine the ⌬G binding value (⌬G binding ϭ ⌬G holo-VDR Ϫ ⌬G apo-VDR Ϫ ⌬G ligand ), where the only default values changed were the cutoff distances, which were changed from 14, 12, and 10 Å, to 10, 8, and 6 Å, respectively. For a more detailed description of the computational techniques/protocols employed herein see the supplemental materials.…”

Annular Structures as Intermediates in Fibril Formation of Alzheimer Aβ17−42

“…Each structure was first subjected to energy minimization for 1000 conjugate gradient steps. At the minimized state, the solvation energy was then calculated using the Generalized Born with a simple switching method (GBSW) 42,43 . Thus, the interaction energy between two dimeric structures was calculated by .…”

Application of solid-state NMR restraint potentials in membrane protein modeling

“…As such, we determined the structures in vacuum as well as in an implicit membrane model in which the average influence of the membrane (waters and lipids) is approximated by solvation free energy terms. As an implicit membrane model, we used a generalized Born model with a simple switching function (GBSW) [26,27] with 0.04 kcal/(mol·Å 2 ) for the surface tension coefficient, 23 Å for the hydrophobic thickness corresponding to a DMPC membrane, and 5 Å for a membrane smoothing length over which the hydrophobic region is gradually changed to the solvent region. The implicit planar membrane is perpendicular to the Z-axis and centered at Z = 0.…”