Toolkit Development Platform

Szmap TK

Szmap TK

Water…where it matters, when it matters

All protein-ligand binding interactions occur in an aqueous environment, therefore predicting the effects of solvent molecules within the binding site is a necessary step in understanding binding affinity. However, the interactions of protein and ligand together with water molecules can have complex and non-obvious effects, which can complicate and obfuscate a lead optimization campaign. The Szmap TK provides the foundation and functionality underlying the SZMAP application that helps modelers and medicinal chemists understand the role of water in molecular interactions such as ligand binding. Using water as a lens, SZMAP can provide the user with insight on critical features of a binding site, predict where and how neighboring waters can influence binding of a ligand, or generate ligand modification hypotheses designed to better exploit specific regions on a binding site. The semi-continuum [1, 2] approach used in SZMAP combines one explicit water molecule with robust continuum solvent methods [3], classical statistical mechanics, and thorough sampling plus the ability to analyze specific water orientations.

For more detailed information on Szmap TK, check out the links below:


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SZMAP

SZMAP calculations identify significant favorable or unfavorable regions of solvent thermodynamics in the binding site. Dominant water orientations are shown, which often match beneficial functional groups on ligands that bind to the protein.

Modeling

The Modeling suite of toolkits provides the core functionality underlying OpenEye's defining principle that shape & electrostatics are the two fundamental descriptors determining intermolecular interactions. Many of the toolkits in the Modeling suite are directly associated with specific OpenEye applications and can therefore be used to create new or extend existing functionality associated with those applications.

  Toolkit Major Functionality
  OEChem TK Core chemistry handling and representation as well as molecule file I/O
  OEDocking TK Molecular docking and scoring
  Omega TK Conformer generation
  Shape TK 3D shape description, optimization, and overlap
  Spicoli TK Surface generation, manipulation, and interrogation
  Szmap TK Understanding water interactions in a bind site
  Szybki TK General purpose optimization with MMFF94
  Zap TK Calculate Poisson-Boltzmann electrostatic potentials

Cheminformatics

The Cheminformatics suite of toolkits provides the core foundation upon which all of the OpenEye applications and remaining toolkits are built. The Cheminformatics suite is a collection of seven individual yet interdependent toolkits that are described in the table below.

  Toolkit Major Functionality
  FastROCS TK Real-time shape similarity for virtual screening, lead hopping & shape clustering
  OEChem TK Core chemistry handling and representation as well as molecule file I/O
  OEDepict TK 2D Molecule rendering and depiction
  Grapheme™ TK Advanced molecule rendering and report generation
  GraphSim TK 2D molecular similarity (e.g. fingerprints) 
  Lexichem TK  name-to-structure, structure-to-name, foreign language translation 
  MolProp TK Molecular property calculation and filtering 
  Quacpac TK Tautomer enumeration and charge assignment
  MedChem TK Matched molecular pair analysis, fragmentation utilities, and molecular complexity metrics

References

  1. Calculation of the thermodynamic properties of aqueous electrolytes to 1000.degree.C and 5000 bar from a semicontinuum model for ion hydration Tanger, J.C., Pitzer, K.S., J. Phys. Chem. 1989, 93, 4941-4951.
  2. Continuum based calculations of hydration entropies and the hydrophobic effect Rashin, A.A., Bukatin, M.A., J. Phys. Chem. 1991, 95, 2942-2944.
  3. A Smooth Permittivity Function for Poisson-Boltzmann Solvation Methods Grant, J.A., Pickup, B., Nicholls, A., J. Comp. Chem. 2001, 22, 608-640.