What information do I need to justify my drug discovery software renewal?
Justifying software renewal requires more than highlighting features; you need quantifiable ROI data that resonates with budget holders. Whether it’s…
We report a new method for X-ray density ligand fitting and refinement that is suitable for a wide variety of small-molecule ligands, including macrocycles. The approach (called “xGen”) augments a force field energy calculation with an electron density fitting restraint that yields an energy reward during the restrained conformational search. The resulting conformer pools balance goodness-of-fit with ligand strain. Real-space refinement from pre-existing ligand coordinates of 150 macrocycles resulted in occupancy-weighted conformational ensembles that exhibited low strain energy. The xGen ensembles improved upon electron density fit compared with the PDB reference coordinates without making use of atom-specific B-factors. Similarly, on nonmacrocycles, de novo fitting produced occupancy-weighted ensembles of many conformers that were generally better-quality density fits than the deposited primary/alternate conformational pairs. The results suggest ubiquitous low-energy ligand conformational ensembles in X-ray diffraction data and provide an alternative to using B-factors as model parameters.
Justifying software renewal requires more than highlighting features; you need quantifiable ROI data that resonates with budget holders. Whether it’s…
Set up for success with hands-on training sessions We start with dedicated training sessions where you and your team get…
Nearly all computational methods in the CADD field depend on parameters whose values are derived from various types of experimental…