Revised electrostatics from invariom refinement of the 18-residue peptaibol antibiotic trichotoxin A50E

Detailed functional understanding of the action of biological macromolecules is reliant on high-quality, accurate data describing their atomic and electrostatic structural properties. We present the application of cutting-edge modeling techniques to the 18-residue peptaibol antibiotic trichotoxin A50E [J. K. Chugh, H. Bruckner and B. A. Wallace, Biochemistry, 2002, 41, 12934] for which low temperature X-ray data (T = 150 K) at subatomic resolution were retrieved from the Protein Databank. Use of aspherical scattering factors (invarioms) enables refinement of individual coordinates and anisotropic displacement parameters unconstrained and standard uncertainties can be estimated by inversion of the full least-square matrix. However, application of the invariom method to model the electron density of trichotoxin A50E has not only improved the structural model in terms of geometry, figures of merit and anisotropic displacement parameters, but also results in the direct calculation of an ab initio quality electrostatic potential and associated dipole moment. Disagreement with previously published electrostatics and possible functional implications are discussed.