How does your feedback shape new StarDrop features?
In the fast-paced world of drug discovery, your time is precious. You’re under pressure to design better compounds, do it…
Abstract
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.
More publications to browse
Switching to StarDrop is easy: Your step-by-step guide
If your current software has hidden costs, performance that can’t keep pace, poor support, or limited visualisation options, it might be time for a change. The good news is, switching to StarDrop is easier than you may think and this guide will walk you through every step.
Why does conformational flexibility matter in drug design?
What are conformational ensembles? A conformational ensemble is a collection of the different 3D shapes a molecule can adopt in…
