Derivation of net atomic charges from molecular electrostatic potentials

Woods, Robert J.; Khalil, Mohamed; Pell, W.; Moffat, S. H.; Smith, Vedene H.

doi:10.1002/jcc.540110304

Cited by 153 publications

(96 citation statements)

References 24 publications

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“…49 Although the atom-centered MEP-derived point charges provide a clear interpretation of the electrostatic properties and are computationally inexpensive, they can poorly reproduce the anisotropic electronic features (e.g., lone pairs, π-systems), 50,51 and also suffer from several technical difficulties. The optimized values of the point charges not only depend on the grid density and size, or the spatial orientation of the molecule relative to the Cartesian axes, 48,[52][53][54][55][56] they also can be inconsistent even across very similar molecules, at odds with the fundamental chemical concept of the transferability of atomic properties. Not only the MEP-fitted charges for atoms of a common functional group in chemically similar molecules may be very different, the charges obtained for the conformers of the same molecule often vary by more than one electron unit.…”

Section: Introductionmentioning

confidence: 99%

Genetic Algorithm Optimization of Point Charges in Force Field Development: Challenges and Insights

2015

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Evolutionary methods, such as genetic algorithms (GAs), provide powerful tools for optimization of the force field parameters, especially in the case of simultaneous fitting of the force field terms against extensive reference data. However, GA fitting of the nonbonded interaction parameters that includes point charges has not been explored in the literature, likely due to numerous difficulties with even a simpler problem of the least-squares fitting of the atomic point charges against a reference molecular electrostatic potential (MEP), which often demonstrates an unusually high variation of the fitted charges on buried atoms. Here, we examine the performance of the GA approach for the least-squares MEP point charge fitting, and show that the GA optimizations suffer from a magnified version of the classical buried atom effect, producing highly scattered yet correlated solutions. This effect can be understood in terms of the linearly independent, natural coordinates of the MEP fitting problem defined by the eigenvectors of the least-squares sum Hessian matrix, which are also equivalent to the eigenvectors of the covariance matrix evaluated for the scattered GA solutions. GAs quickly converge with respect to the high-curvature coordinates defined by the eigenvectors related to the leading terms of the multipole expansion, but have difficulty converging with respect to the low-curvature coordinates that mostly depend on the buried atom charges. The performance of the evolutionary techniques dramatically improves when the point charge optimization is performed using the Hessian or covariance matrix eigenvectors, an approach with a significant potential for the evolutionary optimization of the fixed-charge biomolecular force fields.

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Section: Introductionmentioning

confidence: 99%

Genetic Algorithm Optimization of Point Charges in Force Field Development: Challenges and Insights

2015

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“…The non-bonded parameters for Ag(I), namely the van der Waals radius and the well-depth have been assigned the values r vdw ¼ 1.72 Å and " vdw ¼ 0.050 kcal mol À1 , respectively 29 . Finally, the RESP atomic partial charges 30 for Ag complexes were derived with the ANTECHAMBER module, and the general AMBER GAFF force field was employed to obtain the force field parameters 31 . Equilibrium distances, angles and dihedrals in Ag complexes have been defined according to crystal structure parameters provided by Poyraz et al 16 .…”

Section: Simulationsmentioning

confidence: 99%

Stability and binding effects of silver(I) complexes at lipoxygenase-1

Vrontaki

Leonis

Avramopoulos

et al. 2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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An anti-inflammatory complex of Ag(I), namely [Ag(tpp) Nevertheless, the STD spectra showed that only the complex of salicylic acid is bound to the enzyme. Molecular docking and dynamics were used to complement our study. The complexes were stabilized inside a large LOX-1 cavity by establishing a network of hydrogen bonds and steric interactions. The complex formation with salicylic acid was more favorable. The in silico results provide a plausible explanation of the experimental results, which showed that only the complex with salicylic acid enters the binding cavity.

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“…The CHELPG method 16 includes points between 0 and 2.8 A plus the van der Waals radius. Several other schemes have been suggested, 12,17,19 but normally no points within the van der Waals radii or more than 3᎐7 A from all atoms are used in the fit. Naturally, this arbitrariness in the choice of the potential points will affect the resulting charges.…”

Section: Introduction Olecular Simulation Methods Have Becomementioning

confidence: 99%

“…A point density of 2,500 pointsratom was used, because the charges of all atoms have been shown to be converged at this density. 17,29 Points with a weight of less than y6 Ž .…”

Section: The Chelp-bow Methodsmentioning

confidence: 99%