The ligand preparation module enables you to prepare the input file to be used by PharmScreen by minimizing the input structures, generating a set of conformations for each of them or calculating molecule parameters such as partial charges or atomic contributions to LogP.
Platform compatibility: On Windos and Mac, it is necessary to have Pharmacelera-API running. On Linux, it can work with or without API running (different options will appear if API is running or not).
- Type minimization method
none: No minimization (default).
uff: Molecular mechanics forcefield estimated using general rules based only on the element, its hybridization, and its connectivity.
mmff: "Static" variant of the MMFF94 forcefield, which is characterized by a different parameterization of torsional and out-of-plane interactions geared towards geometry optimization studies.
am1: A semi-empirical method for the quantum calculation of molecular electronic structure. It is based on the Neglect of Differential Diatomic Overlap integral approximation. Specifically, it is a generalization of the modified neglect of differential diatomic overlap approximation.
rm1: A reparameterization of the AM1 model that improves the semiempirical molecular orbital models. It uses the same algorithms of AM1 but C, H, N, O, P, S, F, Cl, Br, and I atom parameters have been changed.
- Generate conformers
Conformer generation is necessary to maximize the chemical space exploration and to consider molecular flexibility as PharmScreen operates with rigid structures.
Conformations can be calculated with other external tools and provided in the input file with the same molecule name for all conformations or generated in this section with the option Generate. Conformers are generated using a distance geometry algorithm. With the default settings the number of conformers changes for each molecule depending on the number of rotatable bonds it has. Also, only those conformers with a minimum RMSD difference of 0.5 Å and a maximum energy value of 6.0 kcal/mol over the most stable conformation are kept.
- Charge Method
none: (Default option). It assumes that partial charges are neither present in the input file or calculated in PharmScreen. Use only if electrostatic field is not used.
userdefined: Use this option when the charges have been precalculated and are included in the input file
gasteiger: (Recommended for standard virtual screening) Fast atom type based method to generate partial charges based on the Gasteiger-Marsili8 parametrization.
am1: Atomic charges derived from the AM1 hamiltonian. The usage of this option is recommended for small sets where accuracy is more important.
esp: This is the electrostatic potential calculation of K. M. Merz and B. H. Besler10. ESP calculates the expectation values of the electrostatic potential of a molecule on a uniform distribution of points. The resultant ESP surface is then fitted to atom centered charges that best reproduce the distribution, in a least squares sense. The usage of this option is recommended for small sets where accuracy is more important.
- LogP Method
none: (Default option) It assumes that LogP values are neither present in the input file or calculated in PharmScreen. Use only if hydrophobic fields are not used.
userdefined: Use this option when the logP parameters has been precalculated and are included in the input file
at: Fast parameters are a simpler model based on ALogP atom types and parametrized with custom values derived from Quantum Mechanical calculations. These parameters are significantly faster but do not take into account molecule conformations or atom types that have not been parametrized.
mst: Quantum Mechanical parameters are derived from semi-empirical (RM1) IEF/PCM-MST solvation models, and are the highest quality descriptors available, although they require more computation time.
- Working Directory
Working directory where screening files are stored. You can enter Windows, Linux or macOS paths.
When using API, a folder name output will be created. All API executions will be saved there with the output name given.
- Output Directory
Name of the folder that contains the outputs of the node.
When using API, a folder name output will be created. All API executions will be saved there with the output name given.
