Department of Theoretical Chemistry

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Ulf Ryde

Professor in Theoretical Chemistry

Research interests

Biochemical molecules studied by theoretical methods

Enzyme mechanisms
The influence of the protein on bound metals, ligands and chromophores
The relation between structure and function of proteins
Ligand-binding affinities
Nature's design of proteins (Why was that metal or amino acid selected?)
QM/MM methods
Combination of QM methods and experimental methods: e.g. crystallographic refinement, NMR, and EXAFS

Selected publications

U. Ryde, M. H. M. Olsson, K. Pierloot & B. O. Roos (1996) "The cupric geometry of blue copper proteins is not strained". J. Mol. Biol. 261, 586-596. DOI: 10.1006/jmbi.1996.0484
U. Ryde, L. Olsen & K. Nilsson (2002) "Quantum chemical geometry optimisations in proteins using crystallographic raw data", J. Comp. Chem., 23, 1058-1070. DOI 10.1002/jcc.10093 .
T. H. Rod & U. Ryde (2005) "Free energy barriers at the density functional theory level: methyl transfer catalyzed by catechol O-methyltransferase", J. Chem. Theory Comput., 1, 1240-1251; DOI:10.1021/ct0501102.
P. Söderhjelm, U. Ryde (2009) "How accurate can a force field become? - A polarizable multipole model combined with fragment-wise quantum-mechanical calculations" J. Phys. Chem. A, 113, 617-627; DOI: 10.1021/jp8073514.

Projects

with references to my list of publications

Ligand-binding affinity
Chlorophyll [88]
Hydrogenase [87]
Development of accurate force fields (NEMO) [86]
Superoxide dismuatases [83,84]
Multi-copper oxidases [77]
QM/MM free energies (QTCP) [75,78,82]
The binding of O₂ to haem proteins [65,70]
Cytochrome P450 [64]
Metallo beta-lactamase [54,69]
Porphyrin metallation and ferrochelatase [53,56,66,72,80]
Cyclams [52]
Quantum refinement and combinations of QM/MM methods with NMR and EXAFS
[47,50,58,62,67,68,73,74,80,81]
Coenzyme B₁₂proteins [46,55,59,61,76]
Electron-transfer proteins (iron-sulphur, cytochromes, and CuA) [42-44]
Carboxylate shifts in zinc proteins [36]
Discrimination between O₂ and CO by myoglobin [31,48]
Methods to determine atomic charges for simulations [25,45]
QM/MM methods [20,40,51,60]
Porphyrin proteins [43,55,57,64,71,79]
Blue copper proteins [21,22,26-30,32,34,35,38-41,43,44,49,63]
Simulations of protein mutants [37]
Calicheamicin [23]
Interpretation of PAC experiments [18,24,33]
Alcohol dehydrogenase [15-17,19,20,24,67]
Oscillations in biochemical systems [7,11-14]
The Calvin cycle [1-6,8-10]

Proteins

blue copper proteins, e.g. plastocyanin, nitrite reducates, and azurin
porphyrin proteins, e.g. myoglobin, Fe/Mg-chelatase, cytochrome P450, cytochromes, peroxidases, catalases, vitamin B12 and coenzyme F430 enzymes
catechol O-methyl transferase
iron-sulphur clusters
superoxide dismuatases (Cu/Zn, Fe, Mn, or Ni)
Ni-Fe and iron-only hydrogenases
multi-copper oxidases
zinc enzymes, e.g. alcohol dehydrogenase, metallo-beta-lactamase, carbanhydrase, thermolysin, and carboxypeptidase

Methods

ab initio quantum chemistry (HF to CASPT2)
density functional theory, preferably B3LYP and BP86/RI
molecular dynamics
molecular mechanics
free energy perturbation
combined quantum chemical and classical methods (QM/MM)
combined quantum chemical and crystallographic refinement methods (Quantum refinement)
QM/MM combined with NMR refinement
QM and QM/MM combined with EXAFS refinement
QM/MM free energy methods (QTCP)
Accurate force fields

Method developments

We develop methods to be used in simulations of proteins. Here are some of them.

ComQum, a combined quantum chemical and molecular mechanical (QM/MM) geometry optimisation program.
ComQum-X , a combined quantum chemical and crystallographic refinement program
ComQum-N, a combined quantum chemical and NMR program
ComQum-EXAFS, a combined quantum chemical and EXAFS program
Chargefit, a program to fit atomic charges to electrostatic moments or potential, e.g. the methods CHELMO and CHELP-BOW.
QTCP, a method for high-level QM/MM free energies

More about software.

Parameterisations

We also have done some parameterisation of protein ligands. These are most of them. Please, contact me if you are interested in the parameters.

A four- or five-coordinate zinc ion with His, Cys, water, and hydroxide ligands. (to be used for alcohol dehydrogenase)
Cu(II) ions with His, Cys, Met, and water ligands; (to be used for blue copper sites, the type 2 copper site in nitrite reductase, and Cu-substituted alcohol dehydrogenase)
Negatively charged Cys
NADH, NAD⁺, NADPH, and NADP⁺
Neutral Arg and Lys
DMSO
SH₂, SH^-, MeSH, MeS^-, EtSH, EtS^-
Xylose

Group members

Former group members

LiHong Hu (postdoc 2010-2011).
Dr. Jimmy Heimdal (PhD student 2006-2010), currently in Copenhagen
Dr. Maryam Farrokhnia (Postdoc 2009)
Dr. Pär Söderhjelm (PhD student 2003-2008), currently PostDoc in Parrinello's group in Lugano.
Dr. Jacob Kongsted (Postdoc 2007-2008), currently in Odense.
Dr. Patrik Rydberg (PhD student 2002-2007), currently in Copenhagen
Dr. Marcus Kaukonen (Postdoc 2006-2008), Currently in Helsinki.
Kambiz Katebzadeh (Project worker 2005-2006)
Aaron Weis (Diploma worker 2005)
Dr. Thomas H. Rod (Postdoc 2003-2005).
Dr. Ya-Wen Hsiao (Postdoc 2003-2005), Currently at AstraZeneca, Södertälje.
Dr. Yong Shen (Postdoc 2003-2004)
Dr. Kasper Planeta Jensen (PhD student 2001-2004), Postdoc Yale university (Jorgensen group). Currently at DTU.
Dr. Lubomir Rulisek (Postdoc 2002-2004), Currently at UOCHB AV CR in Prague, Czech Republic
Dr. Kristina Nilsson (PhD student 1998-2003), "Quantum chemical interpretations of protein crystal structures", Lund, December 12, 2003; Currently at AstraZeneca, Mölndal.
Dr. Torben Rasmussen (Postdoc 2002-2003), Currently at Linköping supercomputer centre.
Dr. Emma Sigfridsson (PhD student 1997-2001), now Emma Evertsson, "Theoretical studies of porphyrin proteins", Lund, September 21, 2001. Currently at AstraZeneca, Mölndal.
Dr. Mats Olsson (PhD student 1995-2000) "Theoretical studies of blue copper proteins", Lund, March 3, 2000. Post doc in A. Warshel's group, University of South California. Postdoc in Jan Jensen's group in Copenhagen.
Jan O. A. De Kerpel (PhD student in Leuven 1995-1999), "Molecular and electronic modeling of blue copper proteins", Leuven Jan 1999. Currently at Devgen, Belgium.
Dr. Conrad Newton (postdoc 1998-1999)
Dr. Antonio Carlos Borin (postdoc 1996-1997), currently in Sao Paolo, Brazil
Dr. Lars Hemmingsen (postdoc 1996), currently at DTU, Lyngby, Denmark

Degrees & Titles

Master of Scence in Chemistry (Dec. 12, 1986)
Doctor of Philosophy in Biochemistry (Oct. 9, 1991)
Docent in Theoretical Chemistry (Mar. 20, 1996)
Assistant Professor (July 1, 1992; Forskarassistent)
Associate Professor (Feb. 1, 2000; Lektor)
Advisor for PhD students at the Chemical Section in Lund university (May 1, 2000- Dec. 12 2001; studierektor)
Senior research position in bioinorganic chemistry, Lund university (July 1, 2001-2007; Särskild forskare)
Professor in Theoretical Chemistry (Mar. 1, 2004)

Hobbies

Music (I play the piano, church organ, and sing in choirs)
Botany (plants, especially blackberries, and fungi)

Links

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