Programming Libraries for Molecular Modeling

Example of a result obtained from a combination of modeling toolkits:
conformers from Omega TK were overlain using Shape TK
while surfaces and coloring were generated by Spicoli TK.

Quacpac TK offers the same features as the QUACPAC application for protomer & tautomer enumeration and charge assignment. Please refer to the QUACPAC product sheet for details.

Omega TK offers the same features as the OMEGA application for conformer generation. Please refer to the OMEGA product sheet for details.

Szybki TK is a general purpose optimizer offering both high-level algorithms for structure optimization against MMFF94 and low-level functions that provide flexibility for dealing with arbitrary functions and coordinate frames. The MMFF94 optimization features are also available in the SZYBKI application - see SZYBKI product sheet for details.

Shape TK is the basis for the ROCS application for shape-based similarity searching. The toolkit allows for fine control over optimization methods, molecule treatment and the nature of the query (grids, generic shapes). Shape TK facilitates the calculation of molecular descriptors for shape (steric multipoles), volume overlap between molecules, and spatial similarity of chemical groups (color force field), as well as the optimization of the latter two quantities.

Examples of use include aligning and comparing protein active sites, performing real-space fitting to electron density, shape fingerprinting [1], consensus shape generation, and discrimination between agonists and antagonists based on shared shapes [2].

Zap TK produces Poisson-Boltzmann electrostatic potentials [3] and, from them, biologically interesting properties including solvent transfer energies, binding energies, pKa shifts, solvent forces, electrostatic descriptors, surface potentials and effective dielectric constants. Zap TK works well for small molecules, proteins and macromolecular ensembles [4]. Unique to Zap TK is a dielectric function based on atom-centered Gaussians [5], which avoids the pitfalls of discrete dielectric constants.

In a study of LCK kinase inhibitors, Zap TK was used to analyse the ligands solvent-exposed portions, simultaneously optimizing solubility and binding affinity [6]. In another study, Zap TK was used for high-throughput MM-PBSA calculations of relative binding free energies [7].

Spicoli TK generates surfaces for molecules and volumes enclosed by these surfaces. Spicoli TK can then apply properties to the surface (hydrogen-bonding, polarity/hydrophobicity, charge etc.) Spicoli TK writes out these surfaces attached to the molecule, so the surface and the molecule can be visualized together.

[1] Haigh, J. A., Pickup, B. T., Grant, J. A., Nicholls, A., J. Chem. Inf. Model., 2005, 45, 673.
[2] Boström, J., Berggren, K., Elebring, T., Greasley, P.J., Wilstermann, M., Bioorg Med Chem., 2007, 15, 4077.
[3] Gilson, M.K., Rashin, A., Fine, R., Honig, B., J. Mol. Biol., 1985, 184, 503;
Jean-Charles, A., Nicholls, A., Sharp, K., Honig, B., Tempczyk, A., Hendrickson, T.F. and Still, W.C., J. Am. Chem. Soc., 1991, 113, 145;
Prabhu, N.V., Zhu, P., and Sharp, K.A, J. Comp. Chem., 2004, 25, 2049.
[4] Menyhard, D.K., and Keseru, G.M., FEBS Lett., 2005, 579, 5392.
[5] Grant, J.A., Pickup, B., and Nicholls, A., J. Comp. Chem., 2001, 22, 608.
[6] Grant, J.A., Rowsell, S., and Timms, D., J. Med. Chem. Lett., 2004, 47.
[7] Brown, S. P., and Muchmore, S. W., J. Chem. Inf. Model, 2006, 46, 999.