Dr. Sherman works closely with researchers using Schrödinger software for molecular modeling and drug design projects. All of the scripts discussed here can be downloaded free of charge from the Scripts page, or by choosing Update from the Scripts menu in Maestro.
Q. I would like to automatically refine my PDB structure using both the force field and the x-ray diffraction data as part of the fitting function. Is there a way to do this with PrimeX?
A. The PrimeX all-atom polish refinement script (primex_polish.py) automates the many steps associated with taking a raw PDB file with x-ray diffraction data and refining it with PrimeX. The final result is an all-atom model that is consistent with the diffraction data, and the script also improves structural properties of the system to be more consistent with force field parameters. The script performs a series of calculations that include hydrogen bond assignment, ligand state generation, ligand placement, and real-space/reciprocal space refinement. Click here for more details of the protocol. Also, the results of applying the all-atom polish refinement script to 94 recently-deposited PDB structures can be found in our recent publication:
Bell, J.A.; Ho, K.L.; Farid, R., "Significant reduction in errors associated with non-bonded contacts in protein crystal structures: automated all-atom refinement with PrimeX," Acta Cryst. D, 2012, D68, 935-952.
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Q. I recently read some papers where they applied an approach called e-Pharmacophore that used the Schrödinger software to develop a pharmacophore model of a receptor binding site based on energetic analysis of ligand interactions. Is there an easy way to do this?
A. Yes, we have an automated workflow to generate e-Pharmacophores, epharmacophores_gui.py. The protocol uses energetic information derived from Glide XP descriptors to rank the importance of pharmacophore features. The work was originally described by Salam et al. in "Novel Method for Generating Structure-Based Pharmacophores Using Energetic Analysis", J. Chem. Inf. Model., 2009 and Loving et al. in "Energetic analysis of fragment docking and application to structure-based pharmacophore hypothesis generation", J. Comp. Aided Mol. Des., 2009.
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