In
drug design applications,
the docking software used for virtual screening and structure-based
ligand design relies on a scoring function. This is an equation that
relates the structure of the docked ligand-receptor complex to the
binding affinity. For practical applications, first-principles
simulation-based methods to compute binding affinity are currently too
computationally demanding whereas general "fast" scoring functions are
often too inaccurate. Tailor-made
scoring functions provide an intermediate route to estimate binding
affinities. The COMBINE (COMparative BINding Energy) analysis method
was developed with the aim of deriving tailor-made, system-specific
scoring functions or QSARs (quantitative structure activity
relationships) that make full use of the structures of receptor-ligand
complexes and
available experimental affinity data, with modest computational
demands. Compared to classical 3D-QSAR methods (such as CoMFA,
GRID/Golpe and CoMSIA), COMBINE analysis makes direct use of structural
information about ligand-receptor binding and therefore can highlight
important
parts of the receptor for binding affinity. In this project,
COMBINE analysis will be applied and developed to address the problem
of designing compounds that are selective between related
protein targets.
Sponsors/Partners:
AstraZeneca R&D Mölndal, Sweden
page last modified: Friday,
13.07.2007
Project Manager
Dr. Rebecca Wade Email:
Phone: +49 (0)6221 - 533 - 247 Fax: +49 (0)6221 - 533 - 298 more >>
