Poster Presentation 2014 International Biophysics Congress

Validation of ligands in X-ray crystal structures (#525)

Alpeshkumar K. Malde 1 , Alan E. Mark 1
  1. The University Of Queensland, Brisbane, QLD, Australia

As of 2014, the Protein Data Bank (PDB) has witnessed deposition of 100,000th structure and is growing rapidly with the advent of high throughout crystallography and structural consortium initiatives. X-ray crystal structures containing at least one of >17,000 organic ligand molecules account for 25% of PDB. Current structure refinement and validation protocols are well suited for biomolecular structures like proteins and nucleic acids, but are far from optimal for non-covalently bound ligands in such structures. The undetected errors and uncertainty in the ligand:protein structures can lead to the misinterpretation of experimental data and possible failure of drug discovery efforts.

I will present case studies on the applications of molecular dynamics simulations and free energy calculations in conjunction with well-validated ligand force field parameters in validating and correcting the structure and binding pose(s) of ligands in X-ray crystal structures.