We have developed methods to obtain accurate structures of active sites of proteins by a combination of experimental and quantum-mechanical (QM) methods. It was first developed using experimental raw-data (structure factors) from X-ray crystallography [1].
Later, it was extended to use experimental data also from NMR or EXAFS measurements [2,3] and we currently work with a similar method for neutron-diffraction data. In essence, we replace the molecular mechanics (MM) potential employed in these methods to supplement the experimental data with more accurate QM calculations for a small but interesting part of the protein.
Thereby, we can actually improve structures obtained with standard methods [4].
Moreover, we can interpret the structures [5], deducing the oxidation state of the metal or the protonation state of protein ligands [6,7], or to detect photoreduction or disorder in the experimental data [8,9].
This information is often essential for the theoretical modelling of the protein.
Ulf Ryde
Lund University
Ulf Ryde
We have developed methods to obtain accurate structures of active sites of proteins by a combination of experimental and quantum-mechanical (QM) methods. It was first developed using experimental raw-data (structure factors) from X-ray crystallography [1].
Later, it was extended to use experimental data also from NMR or EXAFS measurements [2,3] and we currently work with a similar method for neutron-diffraction data. In essence, we replace the molecular mechanics (MM) potential employed in these methods to supplement the experimental data with more accurate QM calculations for a small but interesting part of the protein.
Thereby, we can actually improve structures obtained with standard methods [4].
Moreover, we can interpret the structures [5], deducing the oxidation state of the metal or the protonation state of protein ligands [6,7], or to detect photoreduction or disorder in the experimental data [8,9].
This information is often essential for the theoretical modelling of the protein.
Ulf Ryde received his PhD in Biochemistry from Lund University (Sweden) under supervision of Prof G. Pettersson in 1991. He then moved into the field of Theoretical Chemistry at the same university, where he became a docent in 1996 and full professor 2004. During 2001–2007 he had a senior research position from the Swedish research council. He studies the structure and function of proteins, in particular, metalloproteins, such as blue copper proteins, heme enzymes, vitamin B12 enzymes, hydrogenases, and multi-copper oxidases. He has developed QM/MM methods for an accurate treatment of environmental effects, e.g. using accurate MM force fields with multipole expansions and anisotropic polarisation, and combinations of QM/MM with free-energy methods or experimental approaches, such as X-ray crystallography, NMR, and EXAFS. He also studies and develops methods to calculate ligand-binding affinities, especially using combinations of MM and QM methods.
1. U. Ryde, L. Olsen & K. Nilsson (2002), J. Comp. Chem., 23, 1058-1070.
2. U. Ryde & K. Nilsson (2003) J. Mol. Struct., 632, 259-275.
3. U. Ryde & K. Nilsson, J. Am. Chem. Soc., 125, 14232-14233
4. U. Ryde & K. Nilsson (2003) J. Am. Chem. Soc., 125, 14232-14233.
5. U. Ryde, Y.-W. Hsiao, L. Rulíšek, E. I. Solomon (2007) J. Am. Chem. Soc., 129, 726-727
6. K. Nilsson & U. Ryde (2004), J. Inorg. Biochem., 98, 1539-1546.
7. U. Ryde, C. Greco, L. De Gioia (2010) J. Am. Chem. Soc., 132, 4512-4513
8. P. Söderhjelm & U. Ryde (2006) J. Mol. Struct. Theochem, 770, 199-219.
9. L. Rulíšek & U. Ryde (2006) J. Phys. Chem. B, 110, 11511-11518.