VCharge

VCharge, developed by VeraChem LLC, is a fast and accurate partial atomic charge calculation tool designed for drug-like compounds. It generates "ab initio-like" partial charges that accurately reproduce electrostatic potentials from Hartree-Fock calculations at the 6-31G* level, making it highly valuable for a wide range of molecular modeling and QSAR applications. VCharge is available for both Linux and Microsoft Windows®, with the Windows version including a graphical user interface for ease of use.

VCharge reads and writes SDfiles, processing compounds at typically more than twenty per second on a modern desktop computer. The calculated partial charges are embedded in an easily parsable datablock within the output SDfile. A free companion program, VDisplay, is available for graphical review of results.

Key Strengths

• Accuracy: Produces "ab initio-like" partial atomic charges that accurately reproduce electrostatic potentials from Hartree-Fock 6-31G* calculations (using SBKJC core potentials for iodine), with potentials typically agreeing to within an RMSD of approximately 4 kcal/mol-e.
• Broad Applicability: VeraChem's proprietary parameter set enables charge computation for virtually any stable compound composed of hydrogen, carbon, oxygen, nitrogen, phosphorous, sulfur, fluorine, chlorine, bromine, and iodine. Results are conformation-independent.
• Speed: Processes over twenty compounds per second on a modern desktop computer, making it suitable for large-scale compound libraries.
• Convenience: Reads and writes standard SDfiles; the Windows version includes a graphical user interface, and the free VDisplay program enables graphical review of charge results on both platforms.

Accuracy and Comparison to Other Methods

• VeraChem's newest proprietary parameter set includes new atom types and has been thoroughly optimized, yielding charges that reproduce Hartree-Fock 6-31G* potentials at CHELPG sampling points with an RMSD of approximately 4 kcal/mol-e, compared to ~5 kcal/mol-e for the previous parameter set across a test set of over 350 molecules.
• VCharge is as accurate as much slower methods such as RESP and AM1/BCC relative to 6-31G* potentials, and is substantially more accurate than simpler approaches such as Gasteiger-Marselli.
• VCharge charges are highly compatible with widely used force fields: for the 20 common amino acids, VCharge matches CHARMM22 and AMBER94 with RMSDs of only 0.07 e and 0.10 e, and correlation coefficients of 0.98 and 0.95, respectively. These differences are comparable to the differences between CHARMM22 and AMBER94 themselves, making VCharge appropriate for use with ligands when a protein is treated by either of these force fields.

How VCharge Works

• VCharge is an electronegativity equalization method in which the electronegativity of each atom depends on its atomic number, hybridization, and bonding environment within the molecule.
• Special constraints are applied to prevent excessive charge flow from ionized groups, and the constrained equalization problem is solved using an adaptation of the method of Lagrangian multipliers.
• A unique feature of VCharge is its automatic identification and handling of alternate resonance forms. Atomic electronegativities and hardnesses are averaged over all identified resonance forms, ensuring that chemically equivalent atoms receive equal charges even when their equivalence is not apparent from the single resonance form provided in the input SDfile.
• Ionization and tautomer states are taken as specified in the input SDfile.

Windows Graphical User Interface

• The Microsoft Windows® version of VCharge includes a convenient graphical user interface that integrates VCharge, the VDisplay molecular visualization program, and helpful VCharge support utilities.
• The interface makes it straightforward to run VCharge and review its results without requiring command-line interaction.

VCharge is part of VeraChem's broader suite of small molecule tools, which also includes VConf, VDraw, VMap, VFilter, Vrms, and VDisplay. It is available for Linux and Windows platforms, and licensing information is available directly from VeraChem LLC.