Partial Charges



  • In a covalent bond, there is a presence of a partial charge in the atoms that combine to form a compound. For example in H X 2 O, since O is more electronegative, therefore there is a presence of a partial negative charge around O. Similarly, as H is less electronegative, it has a presence of a partial positive charge around it.
  • Thus, in an HCl molecule, the chlorine atom carries a partial negative charge and the hydrogen atom has a partial positive charge. Figure 2 shows the distribution of electrons in the H–Cl bond. Note that the shaded area around Cl is much larger than it is around H. Compare this to Figure 1, which shows the even distribution of electrons in.

A partial charge usually has a positive or negative non-integer. Each atom in a molecule has both, but in this course, we're only able to calculate the formal charge. For the partial charge, we would use. To know which atom has a positive or negative partial charge in a bond, we need to compare the electronegativity of both atoms in a bond.

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Displaying Dipole Moment

The value of the Dipole Moment is listed Under Calculated Quantities in the Overview section, if calculated. Clicking the view icon () will display the quantity in the 3-D visualizer. The dipole moment is centered at the center of mass and its length is scaled such that 1 Debye corresponds to 1 Angstrom. Its orientation follows the chemistry convention of pointing in the negative direction.

Partial charges water


Dipole Moment

Displaying Partial Charges

The values of the partial charges are listed Under Calculated Quantities in the Partial Charges section, if calculated. They are listed by atom index, which is displayed in the 3-D visualizer by default. Clicking the view icon () will display the partial charges in the 3-D visualizer. When viewing partial charge, the radius of each atom is proportional to its partial charge, and negative atoms are colored red while positive atoms are colored blue.


Partial Charges

The WebMO color convention is that small ↔ large values are mapped onto red ↔ blue colors. To remember this, think about photon energy, i.e., red photonshave less energy thanblue photons!

Introduction¶

Partial charges occur when

The assignment of appropriate atomic partial charges, both to small moleculeligands and to biopolymers (such as proteins and nucleic acids) is essentialto getting meaningful results from any electrostatics calculation.

A molecule may be considered a collection of atomic nuclei and the electronsthat surround them. The number of protons in each nucleus defines its atomicnumber/element. If the number of electrons exactly matches the number ofprotons in these nuclei, the molecule is neutral and has no net charge. Ifthere are more electrons than protons, the molecule has a net negativecharge, and if there are less, the molecule has a net positive charge.

It is both the atomic nuclei and the net charge that define the identity ofa molecule. Indeed, this is a representation common to quantum chemistry.Adding or removing electrons (or atoms) from a molecule produces a differentmolecule.

In the discrete world of cheminformatics, valence bond theory allows theelectrons present in a system to be represented in terms of bonds withformal bond orders, and formal charges assigned to particular atoms. The sumof the formal charges is equal to the net charge on the molecule, but whichatoms are assigned which formal charges can be to some extent arbitrary dueto resonance delocalization. In such casesthe same molecule may be represented by similar connection tables, but withformal charges assigned to different sets of atoms.

For example, guanidinium may be expressed as either N[C+](N)N with theformal charge assigned to the carbon, or as [NH2+]=C(N)N with the formalcharge assigned arbitrarily to one of the otherwise equivalentnitrogens. A similar example is a thiocarboxylate group, where eitherC(=O)[S-] or C(=S)[O-] are both equally appropriate representations of thesame chemical functionality.

A zwitterion is an electrically neutral molecule that is represented ascontaining atoms with positive formal charge as well as atoms with negativeformal charge.

Perhaps the most important fact to appreciate when considering formalcharges on atoms is that they are all artificial constructs by chemiststo accommodate a particular chemical model. A figment of a chemist’s feveredimagination. Like valence bond theory, they are an exceptionally useful and powerfuldiscretized model of the universe. But as with any model of reality, it hasits limitations. Formal charges, for all their numerous benefits to mankind,unfortunately, are not localized on an atom.

The limitations of describing formal charges with valence bond theory isapparent even within cheminformatics. Sydnones, for example, are a class ofheterocyclic compound that cannot be written using normal covalent bondswithout introducing and arbitrarily assigning both positive and negativecharges. Similarly, in inorganic chemistry, the ditechnetium cation,(mbox{Te}_{2}^{+5}), causes similar problems where the +5 formal chargecannot be assigned to both technetium atoms without breaking symmetry.

A better model, or approximation, of the wave function describing thedistribution of electron density around a molecule is the use of atomicpartial charges. A partial charge is a floating-point value assigned to eachatomic center intended to model the distribution of electrons over amolecule.

Atomic partial charges are yet another approximation, much like the formalcharges described above. However, partial charges provide a much bettermodel to describe the electric field, dipole moment and other observableproperties of a molecule.

A common limitation of the use of partial charges is the assumption thatthey are conformationally invariant. Unfortunately, the distribution ofelectrons around a molecule depends upon the spatial configuration of itsnuclei. Some partial charge assignment algorithms, such as the method ofGoddard and Rappé, consider these conformational effects, whilst others thatare based on quantum mechanics, such as the RESP and AM1BCC methods of Baylyet al., go to great lengths to eliminate conformational effects, forexample, by restraining and symmetrizing symmetric atom positions. This isnecessary in order to be able to properly handle multiple conformations and changesin geometry (e.g. geometry optimization) with a single set of atomic charges.

Theory¶

Marsili-Gasteiger Partial Charges¶

Marsili-Gasteiger partial charges are assigned using a two stage algorithm.In the first stage, seed charges are assigned to each atom in the molecule.For example, carboxylate oxygens are each assigned the value -0.5. Duringthe second stage, these initial charges are then shared across bonds, movinga certain amount of charge from one atom to another. The partial chargemoved and its direction is determined by difference in electronegativitiesof the atoms on each end of the bond. The relaxation algorithm is theniterated several times (by default eight passes), attenuating the chargemoved with each iteration. OpenEye does not recommend use of this chargemodel for intermolecular interactions; it was never intended for this purpose.The author of the method (Johann Gasteiger) developed it to comparerelative reactivity of related organic chemical functional groups withindifferent molecular contexts. Here it is included for comparison purposes.

Partial Charges Chem

MMFF94 Partial Charges¶

The partial charges used by the MMFF94 and MMFF94s force fields are assignedusing a four stage algorithm. In the first stage, each atom of the moleculeis assigned an MMFF94 atom type. In the second stage, an initial seedpartial charge is assigned to each atom based upon its atom type. For a fewatom types, the initial partial charge also depends upon the localenvironment. In the third stage, the initial charges assigned to aromaticrings are shared between all atoms of the aromatic ring. Finally, in thefourth stage, a table of bond charge increments (BCI) is used to movecharges across bonds based upon the bond type of the bond (single, double,triple) and the atom types of the atoms at each end. Developed for theelectrostatic interactions within the above-mentioned force fields, theyare the appropriate charges to use with these force fields most notably forintramolecular interactions of pharmaceutical and bio-organic small molecules.They are less well-suited (but still passable) for intermolecular interactionsusing the common two-body additive Coulomb interactions as used in Amber,Charmm, Gromacs. For these better choices would be amber99sb charges onproteins and peptides, and am1bccsym charges on the ligand.

AM1 Charges¶

AM1 charges are a set of Mulliken-type charges derived from a semi-empiricalquantum-mechanical calculation. For further discussion of this method,please see Dewar et. al. These should not be used for intermolecularinteractions of force fields.

Partial Charges Periodic Table

AM1BCC Charges¶

AM1BCC charges start with Mulliken-type partial charges derived from the AM1semi-empirical quantum mechanical (QM) wave-function.In a second stage, bond-charge corrections (BCCs) are appliedto the partial charges on each atom to generate new partial charges. Manydifferent variants of AM1BCC charges are offered within our API because ofthe significant influences of several different factors on theseQM-derived charges. Specifically, these factors are

  • Optimization: whether or not the input geometry is optimized. QMwavefunctions in general are quite sensitive to geometry, especially bondlengths and bond angles, so this can markedly affect the partial charges.In general, optimizing the geometry is recommended. To avoid a collapseof the conformation due to strong intramolecular electrostatic interactions,light restraints to the starting geometry are applied.
  • Symmetrization: whether or not topologically similar atoms (for examplethe two oxygens on a carboxylate) are constrained to have identicalvalues. The true QM wavefunction is usually asymmetric around topologicallysimilar atoms, leading to asymmetric partial charges. However, if the samepartial charges are to be used on different conformers (as with generalfixed-charge force fields) it is important that these charges be symmetrizedor else interconverting between formally degenerate conformers (e.g. 180degree rotation of the carboxylate) will have non-degenerate electrostaticenergies. In general, if the partial charges are to be applied to morethan the single conformer used to generate them, symmetrization is stronglyrecommended.

Partial Charges Chem

Another important issue with AM1BCC charges is if highly conformer-specificcharges are generated which are unsuitable for other conformers, leading toundesirable perturbed electrostatic energies for those other conformers. Toaddress this problem, we strongly recommend the ELF conformer selection protocoldescribed below.

“Standard” AM1BCC includes both optimization and symmetrization.

OpenEye considers AM1BCC charges to be the best partial charge modelcurrently available. For further discussion, please see the work ofChristopher I. Bayly.

ELF Conformer Selection¶

Definition

ELF conformer selection is a method to select one or more conformers havingElectrostatically Least-interacting Functional groups (ELF) from alarge conformer database. The purpose of this method is to resolveimportant issues with QM-derived charges in general, including AM1BCC charges.The issue is that strong short-range intramolecular polarizationsspecific to a certain conformation, as with an intramolecular hydrogen bondor salt bridge, usually leads to strongly perturbed partial charges for the atomsinvolved. These charges can be very different from those found for otherconformers which do not have that intramolecular polar interaction. If suchpartial charges are applied to all conformers, some of those other conformersare very likely to have wrongly over-stabilized solvation energies.

Partial Positive Charge

A second problem arising from this issue is the precision or sensitivity ofthe electrostatic energies resulting from QM-derived charges. By this we mean the variancein electrostatic relative energies between different conformers depending on whatconformer is used for the QM-derived charges. Imagine two different sets ofQM-derived partial charges for a molecule, each coming froma conformer having different strong intramolecular hydrogen bonds. Each set ofpartial charges will have strongly perturbed partial charges for the internallyhydrogen bonded atoms, but they will be different. The relative energiesbetween conformers will be different depending which partial charge set is used.

For these reasons it is important to avoid generating QM-derived partial charges froma conformer having electrostatically strongly interacting functional groups.This is what ELF conformer selection does.

Partial Charges Element

ELF needs to start with enough conformers so that it can finda population of conformers that do not have strongly-interacting functional groups.In the first stage, the Coulomb electrostatic energy is calculatedfor every conformer using the absolute value of the MMFF94partial charges (original negative charges are replaced withtheir absolute values). The electrostatic energies with such chargesdestabilize all strong polar interactions, and thus the lowest electrostaticenergies correspond to the Electrostatically Least-interacting Functionalgroups. The lowest-energy 2% of conformers is selected as the 2% ELF population.We find that averaging 10 diverseconformers from the 2% ELF population is sufficient to providea well-behaved set of QM-derived partial charges even for highly polarand charged molecules.

Partial Charge Calculator

Amber ff94, ff96, ff99, ff99sb, and ff99sbc0 Partial Charges¶

The partial charges used by the AmberFF94 force field are based on fittingquantum mechanical electrostatic potentials (esp). They were developed to addresstwo key issues with earlier esp-fit charge sets: unrealistically high charges on chargecenters and the variation of atomic charges with conformation. While the lattershould have some basis in electronic structure, numerical instability in thecharge fitting process was the source of both these pathologies. AmberFF94 chargesets use restrained esp-fitting (RESP) to control the numerical instabilitiesand simultaneous multi-conformer fitting to lead to conformation-independent chargesthat are restricted to individual residues. Particular attention was given toensure that backbone amides have consistent charges. The Amber force fieldsff94, ff96, ff99, ff99sb, and ff99sbc0 all use the same set of RESP charges, theydiffer in other terms (mostly torsional).