W0225

Enhancements and New Features in X-LIGAND. Zeljko Dzakula, Daniel R. Berard, David Kitson, and Sándor Szalma, Accelrys, Inc. 9685 Scranton Rd. San Diego, CA 92121, USA.

We have been developing new algorithms in order to enhance the performance of the automated protein-ligand crystallographic structure determination software package X-LIGAND. The goal is to improve the convergence of the method, extend its limit on the number of torsions in a ligand, and optimize the analysis of the unsatisfied electron density.

In addition to comparing the tensor of inertia of the unsatisfied density with the tensors of inertia corresponding to the randomly generated conformers, X-LIGAND now extends the analysis of the integral properties of the electron distribution and includes its third moments into the filtering procedure. Unlike the tensor of inertia, the third and higher moments take into account structural details provided by the high-resolution data and enable discrimination between similar portions of the ligand. This improvement also includes a new, more precise rotation algorithm, used to reorient the ligand within the candidate site.

To account for heavy atoms, a new weighting protocol is incorporated into X-LIGAND. It takes into account atomic numbers of the ligand atoms and biases the moments of the distribution (geometric center, tensor of inertia, third moments) toward the heavier atoms. This significantly improves X-LIGAND’s performance when a small number of heavy atoms dominate the unsatisfied density.

Additional protocols currently under development include a choice to truncate electron density overlaps with protein and automated treatment of NCS copies.

Validation studies involving a wide variety of ligands, ranging from rigid to highly flexible, confirms that the newly implemented features enhance the performance of X-LIGAND and extend its applicability.