Xtrapol8: Identifying and modelling low-occupancy states in MX crystallography - Elke De Zitter

Описание: Xtrapol8 is a program that aims to aid structural biologists in identifying and modeling low occupancy states in macromolecular crystallography.1 It was originally written for the analysis of time-resolved crystallography data,
to compare electron density maps and structures acquired before and after the application of a trigger. Nevertheless, Xtrapol8 can also be applied to other cases in which a low-occupancy state is of interest, e.g. ligand binding in which the reference and triggered state refer to the apo and holoprotein, respectively. Xtrapol8 enables visualization of the difference between the reference and triggered states by the calculation of Fourier difference map (Fobs,triggered-Fobs,untriggered).2 Additionally, the program generates extrapolated structure factor amplitudes (Fextrapolated / ESFAs) that solely describe the triggered state.3 These can be used in traditional
crystallographic structure refinement and calculation of electron density maps. Bayesian weighting can optionally be applied to generate improved Fourier difference map or ESFAs.4,5 In all cases, the occupancy of the triggered state needs to be determined to calculate the ESFAs correctly, explaining that another important aspect of Xtrapol8 consists in the estimation of the occupancy based on the electron density maps and automatically refined models. Xtrapol8 can be launched via the command line or controlled with a graphical user interface, and allows control over a large number of parameters, for which defaults have been carefully chosen. Thus, the program is highly adapted to the user’s expertise. During my talk, I will give a brief overview of the program’s operation, good user’s practice and interpretation of the Xtrapol8 outcome.


[1] De Zitter, E., Coquelle, N., Oeser, P., Barends, T. R. M., Colletier, J.-P. (2022), Commun Biol. 5, 640.
[2] Rould, M. and Carter, C. W. (2003), Methods Enzymol., 364, 145-163.
[3] Genick, U. K., Borgstahl, G. E., Ng, K., Ren, Z., Pradervand, C., Burke, P. M., Srajer, V., Teng, T. Y., Schildkamp, W., McRee, D. E., Moffat, K., Getzoff, E. D. (1997), Science, 275, 1471-1475.
[4] Ursby, T. & Bourgeois, D. (1997), Acta Crystallogr. A, 53, 564-575.
[5] Ren, Z., Perman, B., Srajer, V., Teng, T. Y., Pradervand, C., Bourgeois, D., Schotte, F., Ursby, T., Kort, R., Wulff, M., Moffat, K. (2001), Biochemistry, 40, 13788-801.