Related Experiment Videos
RigFit: a new approach to superimposing ligand molecules
C Lemmen1, C Hiller, T Lengauer
1German National Research Center for Information Technology (GMD), Institute for Algorithms and Scientific Computing (SCAI), Sankt Augustin, Germany.
Journal of Computer-Aided Molecular Design
|December 3, 1998
Summary
RIGFIT, a novel molecular alignment tool, enables rapid and accurate superposition of ligands and molecular fragments for drug design. This method facilitates interactive use and database screening, crucial when receptor structures are unknown.
Area of Science:
- Computational chemistry
- Drug discovery
- Structural bioinformatics
Background:
- Drug design often relies on ligand similarity analysis when receptor structures are unknown.
- Accurate mutual ligand superposition is critical for comparative studies.
- Efficient methods for handling conformer sets and database screening are needed.
Purpose of the Study:
- To introduce and evaluate the RIGFIT approach for molecular superposition.
- To assess RIGFIT's performance in approximating known crystal structure orientations.
- To demonstrate RIGFIT's utility in fragment-based drug design and database screening.
Main Methods:
- Utilized the RIGFIT algorithm for mutual ligand and molecular fragment superposition.
- Evaluated RIGFIT's accuracy and speed against a state-of-the-art alignment tool.
- Applied RIGFIT in three test cases: crystal structure orientation approximation, fragment placement, and database screening.
Main Results:
- RIGFIT offers a trade-off between computational time and accuracy.
- Competitive accuracy with existing tools is achieved at approximately 6 seconds per superposition.
- Increased accuracy is attainable with longer computation times.
- Successful application in fragment-based database screening.
Conclusions:
- RIGFIT is an efficient and accurate tool for molecular superposition, particularly valuable in structure-lacking drug design scenarios.
- The method supports interactive use, processing of conformer sets, and database screening.
- RIGFIT, integrated into the FLEXS software, provides a valuable resource for computational drug discovery.