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10:58
Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Predicting protein ligand binding motions with the conformation explorer
Samuel C Flores1, Mark B Gerstein
1Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden. samuel.flores@icm.uu.se
BMC Bioinformatics
|October 29, 2011
Summary
This study presents a novel computational method to predict protein conformational changes upon ligand binding. The approach accurately models hinge-bending motions, crucial for understanding protein function and drug discovery.
Area of Science:
- Structural Biology
- Computational Biophysics
- Drug Discovery
Background:
- Understanding protein-ligand interactions is vital for biological insights and drug design.
- Predicting large-scale protein conformational changes upon ligand binding remains a significant challenge.
Purpose of the Study:
- To develop a computational method for predicting protein conformational changes induced by ligand binding.
- To model hinge-bending motions, a common class of protein dynamics.
Main Methods:
- Hinge region identification between protein domains.
- Application of Euler rotations to simulate domain movements.
- Molecular Dynamics simulations for equilibration and refinement.
- Scoring of generated structures using a fitness function favoring holo conformations.
Main Results:
- The method successfully predicts ligand-bound (holo) conformations for proteins exhibiting hinge-bending motions.
- Iterative refinement of structures minimizes a novel fitness function.
- Accurate prediction of conformational changes for five well-studied proteins.
Conclusions:
- The developed method effectively predicts holo protein conformations from apo structures.
- This approach aids in understanding protein dynamics and facilitates structure-based drug design.
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