DEFORMATION ELECTRON DENSITY AND ATOMIC CHARGES: FROM SMALL MOLECULES TO PROTEIN STRUCTURES

Christian Jelsch, Virginie Pichon-Pesme, Claude Lecomte & Martha Teeter

¹ Laboratoire de Cristallographie et Modélisation des Matériaux Minéraux et Biologiques (LCM3B). Université Henri Poincaré - CNRS BP 239. 54506 Vandoeuvre-les-Nancy Cedex FRANCE E-mail: jelsch@lcm3b.u-nancy.fr
²Merkert Chemistry Center, Boston College, Ma 02167, USA

Accurate xray structure factors at high resolution permit the observation and measurement of the non-spherical character of the electron density (parameterized as multipoles) and of the atomic charges. A database of average multipole and charge parameters has been build in our laboratory from charge density analysis of several peptide crystals [1].

By applying the notion of charge density transferability, a charge density study on the helical octapeptide Ac-Aib₂-L-Lys(Bz)-Aib₂-L-Lys(Bz)-Aib₂-NHMe at 0.8 Ä resolution has been carried out [2]. We will show that the electron density peaks are well defined in the dynamic deformation maps when the thermal motion of the atoms is moderate (B typically lower than 4IJ). In this case, a non-truncated Fourier synthesis of the deformation density requires that the diffraction data are available to resolutions better than 0.9 Ä.

Then, we will present the first results concerning a charge density study of a protein (crambin) [3]. The X-ray data of crambin (46 amino-acids) have been collected by Z. Dauter and M. Teeter at the EMBL Hamburg synchrotron to a resolution of 0.54 Ä at cryogenic temperature. The thermal displacement parameters of the protein atoms are remarkably low ( <B> = 3IJ ). After a conventional structure refinement using anisotropic temperature factors the crystallographic residual is 7.2%.

Then we performed a restrained and constrained multipole refinement [4], the strategy of which will be discussed. The resulting charge density maps and net atomic charges will be shown. In conclusion, future applications in very high resolution protein crystallography will be critically discussed.

[1] Pichon-Pesme V., Lecomte C. & Lachekar H. (1995). J. Phys. Chem., 99, 6242-6250
[2] Jelsch C., Pichon-Pesme V., Lecomte C. & Aubry A.(1998). Acta Cryst D, In Press.
[3] Teeter M.M., Roe S.M. & Heo N.H. (1993). J. Mol. Biol., 230, 292-311.
[4] a) Hansen N.K. & Coppens P. (1978). Acta Cryst., A34, 909-921.
b) Jelsch C & Hansen N.K. (1998) Restrained MOLLY Program.