Improved protein structures by quantum refinement - Ulf Ryde
In standard crystallographic refinement proteins, the experimental data is normally not enough to unambiguously decide the positions of all atoms. Therefore, the crystallographic data are supplemented by a set of empirical restraints that ensure that bond lengths and angles make chemical sense. To obtain more accurate results, we have suggested that this potential can
be replaced by more accurate quantum-mechanical calculations for a small, but interesting part of the protein, giving the method of quantum refinement.[1] We have shown that quantum refinement can locally improve crystal structures,[2] decide protonation state of metal-bound ligands,[3–6] oxidation state of metal sites,[7,8] detect photoreduction of metal ions[7,9] and solve scientific problems regarding what is really is seen in crystal structures.[9–11] Several other groups have implemented this and similar approaches.[12] I will describe the method, show some applications and discuss recent developments, including extensions to cryogenic electron microscopy structures, micro electron-diffraction or serial crystallography.[13]
[1] U. Ryde, L. Olsen, K. Nilsson, 2002, J. Comput. Chem. 23, 1058.
[2] U. Ryde, K. Nilsson J. Am. Chem. Soc. 2003, 125, 14232.
[3] K. Nilsson, U. Ryde, J. Inorg. Biochem., 2004, 98, 1539
[4] L. Cao, O. Caldararu, U. Ryde, J. Phys. Chem B, 2017, 121, 8242.
[5] L. Cao, O. Caldararu, U. Ryde, J. Chem. Theory Comput., 2018, 14, 6653.
[6] O. Caldararu, M. Feldt, D. Cioloboc, M.-C.van Severen, K. Starke, E. Nordlander, et al. Sci. Rep. 2018, 8, 4684
[7] L. Rulíšek, U. Ryde, J. Phys. Chem. B, 2006, 110, 11511
[8] L. Cao, Börner, M. C., Bergmann, J., Caldararu, O. & U. Ryde, Inorg. Chem. 2019, 58, 9672.
[9] P. Söderhjelm, U. Ryde, J. Mol. Struct. Theochem, 2006, 770, 199
[10] L. Cao, O. Caldararu, A. C. Rosenzweig, U. Ryde, 2018, Angew. Chem. Int. Ed., 57, 162.
[11] J. Bergmann, E. Oksanen & U. Ryde, J. Biol. Inorg. Chem. 2021, 26, 341-353.
[12] J. Bergmann, E. Oksanen, U. Ryde, Curr. Opin. Struct. Biol. 2022, 72, 18.
[13] K. J. M. Lundgren, O. Caldararu, E. Oksanen, U. Ryde. IUCrJ. 20234, 11, 921.