The height of structural knowledge is possession of a ligand-protein complex. Even though (due to our poor understanding of large-molecule physics) we can not predict affinities, or even likely trends, from such information such structures do help rationalize medicinal chemistry.

WABE- electrostatics optimization of a lead compound

As well as utility with matching electrostatic profiles to other molecules, WABE can find complementary profiles to active sites. WABE generates analogs by a series of isosteric replacements. It is capable of generating anywhere from 10 to 10,000,000 potential leads, depending on the rules of replacement, which are 'learnt' from chemistries presented to it. Because the shape remains the same, the energies of interaction with the residues in an active site can then be calculated very quickly, with full accounting for desolvation effects via the Poisson equation (~100,000 per second).

Seascape Scientific Partner:OpenEye Scientific Software, New Mexico

Zap- an efficient Poisson-Boltzmann electrostatics solver

Ultimately, one of the hopes for Poisson-Boltzmann technology is to make a contribution to the evaluation of binding energies. To date it has typically been applied naively, i.e. often with poor charge sets, incorrect placements of protons, side chains, incomplete convergence, questionable dielectrics and poor choices of atomic radii. Even so, it often improves trends compared to traditional scoring functions. PB may be limited for binding energies, but the experimental determination has not yet been made.

Seascape Scientific Partner:OpenEye Scientific Software, New Mexico

SZYBKI- fast structure optimization of ligands in gas-phase, solution, or within a protein active site

(It means fast in Polish). The Merck Force Field developed by Halgren et al to still be one of the best force fields available. SZYBKI is OpenEye implementation of MMFF, complete with solvent terms for use in ligand, protein-ligand and protein minimizations.

Seascape Scientific Partner:OpenEye Scientific Software, New Mexico

AFITT- crystallographic refinement and analysis

AFITT has, at its heart, the same concepts as the rest of OpenEye tools: that shape, electrostatics and chemistry matter. For instance, many ligand structures deposited in the PDB are manifestly incorrect (over strained, clashing with the protein, in incorrect chemical forms). The goal of AFITT was to give crystallographers and modelers the tools to over come such problems by including a modern forcefield (MMFF), strong cheminformatics (OEChem) and shape fitting for real space refinement.

Seascape Scientific Partner:OpenEye Scientific Software, New Mexico

VIDA II - molecular visualization and data analysis on very large datasets

Many of OpenEye tools either generate or sift through vast quantities of 3D ligand information, and as such VIDA II is the best program available for large scale visualization. VIDA II can handle small lists of molecules or corporate collections and can view them as multi-pane 3D, 2D depictions, SMILES strings, spreadsheet entries, html forms, graphs and drill-down lists. It can view them in the context of proteins or other small molecules, as simple line models or photo-realistic balls and sticks. With a python core VIDA II is easily scriptable and can be tailored to many end-uses. Works, naturally, on many platforms.

Seascape Scientific Partner:OpenEye Scientific Software, New Mexico



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