ChargeCalculator:FAQ

What is the physical meaning of atomic charges?

Atomic charges, or atomic partial charges, are non-integer numbers quantifying the balance of positive (nuclear) charge and negative (electronic) charge associated with each atom. In the 3D space, atomic charges represent points placed at the position of the atomic nuclei, and may be termed atomic point charges. The molecular representation based on atomic point charges is thus a very basic abstraction of the molecular electron density.

Atomic charges are conceived to reflect the uneven distribution of electron density in the molecule. While atomic charges are merely concepts and not physical observables, they have been used heavily in theoretical and applied chemistry due to their highly intuitive character and correlation with measurable quantities such as the electrostatic potential, polarity, reactivity, etc. Nowadays, atomic charges are still integral parts of many modeling applications, and are still used in reasoning basic chemical processes.

When employing atomic charges, you must be aware of the limitations inherent to the atomic point charge model. A single number can give an idea about whether there is more electron density around some atoms compared to others, but it cannot characterize the actual distribution of electron density in the space between the atomic nuclei. Thus, all properties which flow from this distribution (such as multipole moments) are generally not well described using atomic charges.

There are more NMR states (models) in my file. Can I run ACC on all, or just a few selected states?

ACC can run on any number of molecules at a time, but each molecule must be uploaded in a separate file. Therefore, you must first separate your initial file into multiple files, each containing a single NMR state of interest to you. Archive these files as .zip. Upload the .zip archive with all models into ACC, and you can compute atomic charges for all models in a single ACC run.

For example, say you have a .pdb file containing 15 NMR models, and you wish to run ACC for models 1-5. Copy the records belonging to model 1 into a file called model1.pdb. Then the records belonging to model 2 into a file called model2.pdb. Continue till model 5, either manually or via a script. Put these 5 files with unique names into a .zip archive, which you can then upload into ACC. Once you upload, you will see that ACC has detected each of the models separately.

After uploading my molecule, I got a warning about "unknown chemical element names". How will it affect my calculation?

EEM, the empirical approach used by ACC to calculate atomic charges, operates with atom types based on chemical elements. When uploading the input file, ACC needs to establish the chemical element of each atom, so that it can assign a suitable atom type, and subsequently EEM parameters. ACC expects to find the chemical element at a pre-defined position in the input file, which depends on the formal guidelines established for each file format. For example, in .pdb files, ACC looks for the chemical element in the column after occupancy and temperature factor (positions 77-78).

ACC holds a predefined list of chemical elements from the periodic table of chemical elements. If ACC does not recognize the chemical element for an atom at the expected position in the input file, it will not include this atom in the atomic charge calculation because it cannot assign an atom type, and therefore EEM parameters. This means that the calculation will run only on the remaining atoms, and when you view the results the atomic charge value for the atoms with unknown chemical elements will be "NaN". If none of the chemical elements are recognized (e.g., the file format guidelines are not respected, or the input file comes from a modeling program which uses the element column to store its own atom types), you will get an error for the entire calculation. Finally, if the input file comes from a modeling program which uses the element column to store its own atom types, and these atom types overlap with known chemical elements, it is possible that ACC includes the atoms in the calculation, but it assigns wrong atom types. For example, if "Ca" appears in the element column, ACC will interpret it as calcium even if it was originally meant as C-alpha.

You can circumvent these issues and make sure these atoms are included in the calculation correctly either by fixing the input file, or using a custom EEM parameter set. The first solution is to adjust the element column in the input file so that it really displays chemical elements. Additionally, make sure the input file format follows the formal guidelines. The second solution is to use an EEM parameter set in which you include EEM parameters for the atoms with unknown chemical elements. By doing so you actually define new atom types and corresponding EEM parameters. For example, say your input file contains hydrogen atoms identified in the element column as "H1" and "Ho", depending on their binding partner. ACC will report them as unknown chemical element names warnings. You may create a new EEM parameter set based on one of the built-in sets already available in ACC (see below how to do that). Copy/paste the parameter information for hydrogen (all text enclosed in the Element tags) twice more into this new parameter set. Then change the Element name tag in one case to "H1", and in the other to "Ho". Save the new set with a unique name and select it from the list. When you start your computation, the atoms with the previously unknown element names "H1" and "Ho" will now be included in the calculation, and treated by EEM parameters suitable for hydrogen.

After uploading my molecule, I got the warning "Atoms in the residue contain multiple names". How will it affect my calculation?

This generally occurs if the chain ID is not explicitly included in the input file, but the molecule contains multiple chains with overlapping residue serial numbers. Since no chain IDs are available, ACC assumes that everything belongs to one chain. When it reads atoms with a residue serial number that has already been loaded, it basically overwrites the composition of the residue with that serial number. Consequently, the computation will run, but the results will not be meaningful for the affected residues, and possibly even for neighboring residues.

ACC provides check chain ID warnings both before and after the computation if this problem is detected, so that the input file can be corrected. Depending on how you generated the input file, this problem may or may not occur. For example, if your structure has multiple chains, and you plan to use the pdb2pqr server to add H to your structure and save it in .pqr format, you must remember to tick the option Add/Keep chain IDs in the pqr file in order to produce correct output.

All of the built-in EEM parameter sets report warnings about Missing Atoms. How does it affect my calculation?

EEM, the empirical approach used by ACC to calculate atomic charges, operates with atom types based on chemical elements. When uploading the input file, ACC needs to establish the chemical element of each atom, so that it can assign a suitable atom type, and subsequently EEM parameters. ACC expects to find the chemical element at a pre-defined position in the input file, which depends on the formal guidelines established for each file format.

It may happen that ACC does not recognize the chemical element (see above why), or there are no EEM parameters associated with that chemical element. In this case, the atom in question will not be included in the atomic charge calculation. This means that the calculation will run only on the remaining atoms, and when you view the results the atomic charge value for the atoms for which there were no EEM parameters will be "NaN". If none of the atoms can be assigned suitable EEM parameters, you will get an error for the entire calculation.

If none of the built-in EEM parameter sets contains parameters for all the atoms in your input molecule, you can circumvent this issue and make sure all atoms are included in the calculation by using a custom EEM parameter set in which you manually include EEM parameters for atoms listed as Missing Atoms. By doing so you actually define new atom types and corresponding EEM parameters. For example, say your input file contains phosphorus. ACC will report Missing Atoms. You may create a new EEM parameter set based on one of the built-in sets already available in ACC (see below how to do that). Copy/paste the parameter information for one of the atoms already present (all text enclosed in the Element tags) once more into this new parameter set. It is good to choose some atom that has similar chemical properties to phosphorus - especially electronegativity and hardness (S would probably be the best choice if available). Change the Element name tag to "P". Inside each Bond Type tag, you will find the values for parameters A and B. You may keep these values, or modify them (see below how to do that). Save the new EEM parameter set with a unique name and select it from the list. When you start your computation, the phosphorus atoms will now be included in the calculation, although the EEM parameters might not be optimal.

The calculation ran, but I got a warning that some atoms were skipped.

EEM, the empirical approach used by ACC to calculate atomic charges, operates with atom types based on chemical elements. When uploading the input file, ACC needs to establish the chemical element of each atom, so that it can assign a suitable atom type, and subsequently EEM parameters. If ACC does not recognize the chemical element (see above why), or no EEM parameters are available for that chemical element, ACC cannot assign EEM parameters to that atom and it will thus be unable to include it in the EEM calculation.

In the final results, the atomic charge for such atoms that are skipped will appear with the value "NaN". These values will not contribute to any of the statistics computed by ACC.

The calculation ran, but I did not obtain any charges.

EEM, the empirical approach used by ACC to calculate atomic charges, operates with atom types based on chemical elements. When uploading the input file, ACC needs to establish the chemical element of each atom, so that it can assign a suitable atom type, and subsequently EEM parameters. If ACC does not recognize the chemical element (see above why), or no EEM parameters are available for that chemical element, ACC cannot assign EEM parameters to that atom and it will thus be unable to include it in the EEM calculation. If this happens with all the atoms in the input file, then no values of atomic charges will be available in the results. In such situations, ACC will report an error.

Why are the charges from different sets so different, and how are these differences relevant?

Explain charge definitions, QM reference data and EEM parameters...

Why do residues have non-integer charge?

Why does the residue charge deviate from the formal values of -1 (negatively charged), 0 (neutral), +1 (positively charged)?

How do I choose the best parameter set?

Discussion above plus what to do with charges...

How do I add parameters if they do not exist?

Explain structure of the xml file; Explain how to approximate parameters (e.g., based on electronegaitivity) Add procedure, copy/paste.

Can I combine parameter sets if I have a biomacromolecule which binds a drug like molecule?

Not really necessary (the parameters for biomolecules seem good enough). Explain how to use chemical elements efficiently.

Can I get good electrostatic potentials?

Some papers report such. Also, some charges better than others...

Can I get dipole moments?

In general, no. The concept of atomic charges has its limitations. Dipoles and higher order multipoles are known to be poorly approximated by a point charge model. You may try though... maybe to compare the dipoles of derivatives of the same molecule...

How is EEM empirical, and how is it related to QM?

Start by having a look at the main terms used by ACC, or return to the Table of contents.