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Theoretical Chemistry

Lund University

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Ulf Ryde, Professor in Theoretical Chemistry

Publications Links Methods GSP Rubus

Research interests

Biochemical molecules studied by theoretical methods

  • Ligand binding
  • The relation between structure and function of proteins
  • Enzyme mechanisms
  • The influence of the protein on bound metals, ligands and chromophores
  • 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. X-ray crystallography, NMR,  EXAFS, neutron crystallography.

Selected publications

  • P. Mikulskis, S. Genheden, U. Ryde (2014) "Large-scale test of free-energy simulation estimates of protein-ligand binding affinities", J. Chem. Inf. Model., 54, 2794-2806; DOI: 10.1021/ci5004027.
  • P. Mikulskis, D. Cioloboc, M. Andrejic, S. Khare, J. Brorsson, S. Genheden, R. A. Mata, P. Söderhjelm, U. Ryde (2014) "Free-energy perturbation and quantum mechanical study of SAMPL4 octa-acid host-guest binding energies", J. Comp.-Aided Mol. Design, 28, 375-400; DOI: 10.1007/s10822-014-9739-x.
  • L. Hu, P. Söderhjelm, U. Ryde "Accurate reaction energies in proteins obtained by combining QM/MM and large QM calculations" J. Chem. Theory Comput. 2013, 9, 640-649; DOI 10.1021/ct3005003.
  • S. Genheden, P. Mikulskis, L. Hu, J. Kongsted, P. Söderhjelm, U. Ryde "Accurate predictions of non-polar solvation free energies require explicit consideration of binding site hydration", J. Am. Chem. Soc., 2011, 133, 13081-13092; DOI 10.1021/ja202972m.
  • P. Söderhjelm, C. Husberg, A. Strambi, M. Olivucci, U. Ryde (2009) "Protein influence on electronic spectra modelled by multipoles and polarisabilities", J. Chem. Theory Comput. 5, 649-658; DOI: 10.1021/ct700347h.
  • 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.
  • 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.
  • 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

Projects

with references to my list of  publications
  • Computational estimates for ligand-binding using FEP [153,196,200], MM/PB(GB)SA [90,117,134,141,147,172,173,174,179,185,195,204], LIE [164,174], QM methods [114,125,169,196,199,207]; non-polar solvation [145,156]; enthalpy–entropy compensation [197]
  • Mechanisms of Mo-enzymes [128,184,198,201,205]
  • Entropies from MD simulations and NMR experiments [143,171,191]
  • Hydrogenases: NiFe [87,194], FeFe [99,100,112,122,138,151,152,155,159,161,162], Fe [190,203]
  • Galectin 3 [126,144,167]
  • Superoxide dismuatases [83,84,123,165]
  • Multi-copper oxidases [77,92,140,148,163,175,180,206]
  • QM/MM methods [20,40,51,60,129,150,181,188]
  • QM/MM free energies (QTCP) [75,78,82,101,106,111,177,206]
  • Parameterisation of MM methods: charges for MM calculations [25,45,120,168]; polarisabilities [154]; metal sites [156]; NEMO [86,97,104]; PMISP [118,125]; Solvation methods [124]
  • Cytochrome P450 [64,89,98,107,110,116,176]
  • Influence of protein on spectroscopic properties [121,149]
  • Metallo beta-lactamase [54,69]
  • Porphyrin metallation and ferrochelatase [53,56,66,72,80,131]
  • Combination of QM methods with X-ray crystallography [47,50,58,62,67,68,74,80,81,94,108,113,136,192], NMR [73] and EXAFS [18,91,96,202]
  • Coenzyme B12 proteins [46,55,59,61,76,119,160]
  • 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]; binding of O2 to haem proteins [65,70]
  • FeS clusters [105,115,133,142]
  • Porphyrin proteins [43,55,57,64,71,79]
  • Blue copper proteins [21,22,26-30,32,34,35,38-41,43,44,49,63]
  • 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]
  • Rubus Sect. Corylifolii [132,137,146,166]

Proteins

  • blue copper proteins, e.g. plastocyanin, nitrite reducates, and azurin
  • Mo enzymes (DMSO reductase, sulfite oxidase, xanthine oxidase)
  • 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)
  • NiFe, FeFe, and Fe 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)
  • Local LCCSD(T0) methods
  • density functional theory, including B3LYP, BP86, PBE, and TPSS
  • 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, parametrisation

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
  • Accurate parametrisations (PON)

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
  • Xylose
  • Numerous protein ligands

Current group members

  • Lili Cao (PhD student 2016-2020)
  • Octav Caldararu (PhD student 2015-2019)
  • Majda Misini Ignjatovic (PhD student 2015-2019)
  • Geng Dong (PhD student 2014-2018)
  • Martin A. Olsson (PhD student 2014-2018)
  • Francesco Manzoni (PhD student, shared with Derek Logan, Biochemistry, 2013-2017)

Former group members

  • Dr. Paulius Mikulskis (PhD student 2011-2015); currently in Nottingham.
  • Dr. Jilai Li (Postdoc 2011-2012), currently in Berlin.
  • Dr. Samuel Genheden (PhD student 2008-2012), currently in Göteborg.
  • Dr. Marie-Céline van Severen (Postdoc 2009-2011).
  • LiHong Hu (Postdoc 2010-2011).
  • Dr. Jimmy Heimdal (PhD student 2006-2010), currently at Max in Lund.
  • Dr. Maryam Farrokhnia (Postdoc 2009).
  • Dr. Pär Söderhjelm (PhD student 2003-2008), currently at Biophysical Chemistry, Lund.
  • Dr. Jacob Kongsted (Postdoc 2007-2008), currently in Odense.
  • Dr. Patrik Rydberg (PhD student 2002-2007), deseased in 2013.
  • 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), currently at ESS in Copenhagen.
  • Dr. Ya-Wen Hsiao (Postdoc 2003-2005).
  • Dr. Yong Shen (Postdoc 2003-2004).
  • Dr. Kasper Planeta Jensen/Kepp (PhD student 2001-2004), 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.
  • 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. Currently 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 and 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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Contact

Phone
+46-46-222 45 02
E-mail
ulf [dot] ryde [at] teokem [dot] lu [dot] se
Fax
+46-46-222 86 48