Ligand & Structure-Based Descriptors
A practical, efficient solution for rank-ordering compounds and predicting binding affinities
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Ligand & Structure-Based Descriptors:
Rank-ordered predictions of ligand binding affinities can be invaluable for drug
discovery, but creating a reliably predictive model can be a
time-consuming endeavor with no guarantee of success. Schrödinger's
Ligand & Structure-Based Descriptors (LSBD) module streamlines this
process by integrating multiple computational applications under a
single interface. With the ability to calculate a wide range of
molecular descriptors, LSBD allows chemists to improve the accuracy of
their predictive models with efficiency and ease.
Within a single run researchers can process a ligand set using one or more of the five theoretical methods encompassed by LSBD. Prime MM-GBSA and MacroModel
eMBrAcE can rank-order ligands, LiaisonScore can be used to estimate
absolute ligand binding affinity, while descriptors can be generated
for linear interaction (LIA) or extended linear response (ELR)
predictions. With the aid of Strike, Schrödinger's statistics module, descriptors are readily correlated
with experimental values to predict absolute binding affinities.
LSBD's straightforward interface allows calculations to be set up with just a
few clicks. Computed energetic terms and structural descriptors are
compiled in a single structure file, making it trivial to pipeline
results to other programs or share results with colleagues. The LSBD
computational workflow is driven by a single keyword-pair input file,
which makes it easy to modify, extend, or repeat calculations in the
future.
Using
the LSBD interface shown above, researchers can easily set up
calculations to generate descriptors with the following programs:
- MacroModel: Ligand binding affinities can be rank-ordered or predicted with the aid of MacroModel eMBrACe calculations.
- Prime: LSBD provides an intuitive interface for running Prime MM-GBSA calculations.
- Liaison: Linear interaction (LIA) descriptors can be calculated with Liaison.
Additionally, the LiaisonScore empirical scoring function provides an
estimate of ligand binding affinity.
- QikProp: With the ability to predict over 35 pharmaceutically relevant ADME
properties, QikProp can be used in conjunction with other descriptors
from LSBD to generate extended linear response (ELR) models that
predict ligand binding energies.
