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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.
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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
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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
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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
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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
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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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