Computational Molecular Biophysics

Jan H. Jensen, Research Associate Professor (Skou Fellow)

Department of Chemistry
University of Copenhagen

Universitetsparken 5
2100 Copenhagen

Denmark

 

Other affiliations: Nano-Science Center

E-mail: jhjensen@kemi.ku.dk
Phone: +45 35 32 02 39
Fax: +45 35 32 02 14

 

Research in the Jensen group is in the area of computational molecular biophysics
- at the intersection of molecular physics, quantum chemistry, and structural biology and structural bioinformatics.
Our work involves, in roughly equal parts, theory/algorithm development and computational modeling of protein chemistry.

 [CV] [Research] [group members] [publications]

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 A more up-to date description of research can be found here

Projects

 

Theory and Algorithm Development

Much of our work is based on the
Effective Fragment Potential Method
a QM/MM method that we co-develop with Mark Gordon at Iowa State University

I am also “consulting” a little on a GUI to GAMESS called Avogadro

 

Protein pKa Prediction

The chemistry of biomolecules is intimately tied to their protonation states and, therefore, to the pKa's of the ionizable functional groups in the molecules.

We have developed a QM/MM based methodology for the prediction of pKa's of ionizable groups in proteins

The QM/MM studies have lead to quantitative structure/activity relationships which forms the basis of our PROPKA program

 

 

NMR Chemical Shifts in Proteins

NMR chemical shifts provide a powerful experimental probe of hydrogen bonding within proteins

We have developed a computational methodology for the accurate prediction of proton chemical shifts in proteins 

We are using the method to rationalize unusual NMR chemical shifts in proteins

 

 

Drug Design

Inhibitors of certain serine proteases are proven antitumor agents, and we are extending the computational methodology for pKa predictions to the calculation of inhibition constants, in order to aid the design for more potent and selective drugs

 

Redox Potentials

The redox potential is a reflection of the electronic structure of the transition metal atom, which in turn is influenced by the nature of the ligands and the protein environment in a way that is not well understood.

QM/MM methods offer a unique opportunity to study redox potentials from first principles and derive quantitative structure/activity rules governing redox potentials in proteins.


 

 

 

Complete Publication List

2008

67. Laura L. Parker, Claudio J. Margulis, and Jan H. Jensen “Rationalization of the Difference in Lifetime of Two Covalent Sialosyl-Enzyme Intermediates in Trypanosoma rangeli Sialidase”, Journal of Physical Chemistry B 2008, 112, 11808-11816.

66.Dmitri G. Fedorov, Jan H, Jensen, Ramesh C. Deka, Kazuo Kitaura “Covalent bond fragmentation suitable to describe surfaces in the fragment molecular orbital method” Journal of Physical Chemistry A 2008, 112, 14093-14095

65. Annette Langkilde, Søren M. Kristensen, Leila Lo Leggio, Anne Mølgaard, Jan H. Jensen, Andrew R. Houk, Jens-Christian Navarro Poulsen, Sakari Kauppinen, and Sine Larsen “Short hydrogen bonds in proteins: A case study of Rhamnogalacturonan acetylesteraseActa Crystallographica Section D 2008, 64, 851-863.

 

64. Aleksander Cehovin, Hector Mera, Jan H. Jensen, Kurt Stokbro and Thomas B. Pedersen “Role of the virtual orbitals and HOMO-LUMO gap in mean-field approximations to the conductance of molecular junctions”, Physical Review B 2008, 77, 195432.

 

63. Jan H, Jensen “Calculating pH and salt dependence of protein-protein bindingCurrent Pharmaceutical Biotechnology, 2008, 9, 96-102.  (Invited contribution: special issue on protein-protein and protein-membrane interactions.)

 

62. Delphine C. Bas, David M. Rogers, and Jan H. Jensen “Very fast prediction and rationalization of pKa values of protein-ligand complexesProteins: Structure, Function, and Bioinformatics 2008,73, 765-783.

 

61. Aaron C. Mason and Jan H. Jensen “Protein-Protein binding is often associated with changes in protonation stateProteins: Structure, Function, and Bioinformatics 2008, 71, 81-91.

2007

60. Jonas Baltrusaitis, Jennifer D. Schuttlefield, Elizabeth Zeitler, Jan H. Jensen and Vicki H. Grassian “Surface Reactions of Carbon Dioxide at the Adsorbed Water – Oxide InterfaceJournal of Physical Chemistry C 2007, 111, 14870-14880.

 

59. Jacob Kongsted, Ulf Ryde, James Wydra, and Jan H. Jensen “Prediction and rationalization of the pH-dependence of activity and stability of family 11 xylanasesBiochemistry 2007, 46, 13581-13592.

 

58. Jonas Baltrusaitis, Jennifer Schuttelfield, Jan H. Jensen, and Vicki H. Grassian “FTIR Spectroscopy Combined with Quantum Chemical Calculations to Investigate Adsorbed Nitrate on Aluminum Oxide Surfaces in the Presence and Absence of Co-Adsorbed WaterPhysical Chemistry Chemical Physics 2007, 9, 4970-4981.

 

57. Junchao Xia, Ryan P. Daly, Feng-Chuan Chuang, Laura L. Parker, Jan H. Jensen, and Claudio J. Margulis “Sugar folding: A novel structural prediction tool for oligosaccharides and polysaccharides IIJournal of Chemical Theory and Computation 2007, 3, 1629-1643.

 

56. Junchao Xia, Ryan P. Daly, Feng-Chuan Chuang, Laura L. Parker, Jan H. Jensen, and Claudio J. Margulis “Sugar folding: A novel structural prediction tool for oligosaccharides and polysaccharides IJournal of Chemical Theory and Computation 2007, 3, 1620-1628.

 

55. Todd J. Dolinsky, Paul Czodrowski, Hui Li, Jan H. Jensen, Jens E. Nielsen, Gerhard Klebe, Nathan A. Baker “PDB2PQR:  Expanding and upgrading automated preparation of biomolecular structures for molecular simulations”, Nucleic Acid Research, 2007,  35, W522-W525.

 

54.Mark S. Gordon, Lyuda Slipchenko, Hui Li, and Jan H. Jensen “The effective fragment potential: a general method for predicting intermolecular interactionsAnnual Reports in Computational Chemistry 3, 177-193, 2007.

 

2006

 

53. Pan-Fen Wang, Allen J. Flynn, Mor M. Naor, Jan H. Jensen, Guanglei Cui, Kenneth M. Merz, Jr., George L. Kenyon and Michael J. McLeish "Exploring the Role of the Active Site Cysteine in Human Muscle Creatine Kinase" Biochemistry 2006, 45, 11464-11472.

 

Michael E. Colvin, Christopher J. Cramer, Clifford E. Dykstra, Jan H. Jensen, Samuel Krimm, Jean-Louis Rivail, Ajit J. Thakkar, and Manuel Yanez "Molecular Quantum Mechanics to Biodynamics: Essential Connections" THEOCHEM 2006, 764, 1-8. (Viewpoint Article; Non-reviewed but still worth reading)

 

52. Laura L. Parker, Andrew R. Houk, and Jan H. Jensen "Cooperative Hydrogen Bonding Effects are Key Determinants of Backbone Amide Proton Chemical Shifts in Proteins" Journal of the American Chemical Society 2006, 128, 9863-9872.

 

51. Baoyu Hong, Majd Haddad, Frank Maley, Jan H. Jensen, Amnon Kohen "Hydride transfer vs hydrogen radical transfer in thymidylate synthase" Journal of the American Chemical Society 2006, 128, 5636-5637.

 

50. Hui Li, Mark S. Gordon, and Jan H. Jensen "Charge transfer interactions in the effective fragment potential method", Journal of Chemical Physics 2006, 124, 214108.

 

49. Jonas Baltrusaitis, Jan H. Jensen, and Vicki H. Grassian "FTIR Spectroscopy Combined with Isotope Labeling and Quantum Chemical Calculations to Investigate Bicarbonate Formation Following Reaction of Carbon Dioxide with Surface Hydroxyl Groups on Fe2O3 and Al2O3" Journal of Physical Chemistry B 2006, 110, 12005-16.

 

48. Nathan Powers and Jan H. Jensen "Chemically Accurate Protein Structures: Validation of Protein NMR Structures by Comparison of Measured and Predicted pKa Values" Journal of Biomolecular NMR 2006, 35, 39-51. (Recommended on Facultyof1000.)

 

47. Dmitri Fedorov, Katzuo Kitaura, Hui Li, Jan H. Jensen, and Mark S. Gordon "The polarizable continuum model (PCM) combined with the fragment molecular orbital method (FMO) " Journal of Computational Chemistry, 27, 976-985.

 

46.      Melissa A. Porter, Jordan R. Hall, James C. Locke, Jan H. Jensen and Pablo A. Molina "Amide Backbone Interactions are the Prime Determinants of Carboxyl pKa Values at N-termini of alpha-helices" Proteins: Structure, Function, and Bioinformatics, 63, 621 - 635.

 

2005

 

45. George A. Kraus, Ning Zhang, Jingqiang Wei, and Jan H. Jensen "Regiochemical Control by Remote Substituents. A Selective Synthesis of Angularly-Fused Ring Systems" European Journal of Organic Chemistry 2005, 3040-3044.

 

44. Jan H. Jensen, Hui Li. Andrew D. Robertson, and Pablo A. Molina "Prediction and Rationalization of Protein pKa Values Using QM and QM/MM Methods", Journal of Physical Chemistry A 2005, 109, 6634-6643 (invited Feature Article; 10th most accessed JPCA article July-Sept, 2005). PDF

43. Hui Li, Andrew D. Robertson, and Jan H. Jensen "Very Fast Structure-Based Prediction and Rationalization of Protein pKa Values" Proteins: Structure, Function, and Bioinformatics 2005, 61, 704-721. PDF.

2004

42. Mor M. Naor and Jan H. Jensen "The Determinants of Cysteine pKa values in Creatine Kinase and a1-Antitrypsin", Proteins: Structure, Function, and Bioinformatics 2004, 57, 799-803.  PDF

41. Hui Li and Jan H. Jensen "Improving the Accuracy and Efficiency of Geometry Optimizations with the Polarizable Continuum Model: New Energy Gradients and Molecular Surface Tesselation", Journal of Computational Chemistry, 2004, 25, 1449-1462. PDF

40. Hui Li, Simon P. Webb, Joseph Ivanic, and Jan H. Jensen "The Determinants of the Relative Reduction Potentials of Type-1 Copper Sites in Proteins" Journal of the American Chemical Society 2004, 126, 8010-8019. PDF

39. Hui Li, Andrew D. Robertson, and Jan H. Jensen "The Determinants of Carboxyl pKa Values in Turkey Ovomucoid Third Domain" Proteins: Structure, Function, and Bioinformatics, 2004, 55, 689-704. PDF (Recommended on Facultyof1000.)

2003

38. Pablo A. Molina, Hui Li, and Jan H. Jensen "Intra-Protein Electrostatics From First Principles: Divide-and-Conquer Methods for QM/MM Calculations" Journal of Computational Chemistry, 2003, 24, 1971-1979. PDF

37. Pablo A. Molina and Jan H. Jensen "A Predictive Model of Strong Hydrogen Bonding in Proteins: The Nd1-H-Od1 Hydrogen Bond in Low-pH a-Chymotrypsin and a-Lytic Protease" Journal of Physical Chemistry B 2003, 107, 6226-6233. PDF

36. Jui-Hsien Huang, Jeffrey J. Luci, Ting-Yu Lee, Dale C. Swenson, Jan H. Jensen, and Louis Messerle "A Planar Tetracoordinate Carbon and Unusual Bonding in an Organodimetallic Propynylidene Complex Arising from Double C-H Activation of an Allene Ligand" Journal of the American Chemical Society 2003, 125, 1688-1689. PDF

35. Hui Li, Christian S. Pomelli, and Jan H. Jensen "Continuum Solvation of Large Molecules Described by QM/MM: Semi-Iterative Implementation of the PCM/EFP Interface", Theoretical Chemistry Accounts 2003, 109, 71-84. PDF

34. Pablo A. Molina, R. Steven Sikorski, and Jan H. Jensen, "NMR Chemical Shifts in the Low-pH Form of a-Chymotrypsin. A QM/MM and ONIOM-NMR Study" Theoretical Chemistry Accounts 2003, 109, 100-107. Special issue on QM/MM methods. PDF

2002

33. Amnon Kohen and Jan H. Jensen "Secondary Swain-Schaad Relations as an Indication for Tunneling in Enzymatic Reactions" Journal of the American Chemical Society 2002, 124, 3858-3864. PDF

32. Hui Li and Jan H. Jensen "Partial Hessian Vibrational Analysis: the Localization of the Molecular Vibrational Energy and Entropy" Theoretical Chemistry Accounts 2002, 107, 211-219. PDF

31. Hui Li, Alexander Hains, Joshua Everts, Andrew D. Robertson, and Jan H. Jensen "The Prediction of Protein pKa's Using QM/MM: The pKa of Lysine 55 in Turkey Ovomucoid Third Domain" Journal of Physical Chemistry B 2002,106, 3486 -3494. PDF

2001

30. George A. Kraus, N. Zhang, A. Melekhov, Jan H. Jensen "Regiochemical Control by Remote Substituents. A Direct Synthesis of Tetrangulol" SYNLETT 2001, pages 521-522.

29. Jan H. Jensen "Intermolecular Exchange-Induction and Charge Transfer. Derivation of Approximate Formulas Using Non-Orthogonal Localized Molecular Orbitals" Journal of Chemical Physics 2001, 114, 8775-8783. PDF

28. Ryan M. Minikis, Visvaldas Kairys, and Jan H. Jensen "Effect of Intra-Protein Electrostatics Derived From First Principles: An Effective Fragment Potential Method Study of the Proton Affinity of Lysine 55 and Tyrosine 20 in Turkey Ovomucoid Third Domain" Journal of Physical Chemistry A 2001,105, 3829-3827. PDF

27. Mark S. Gordon, Mark Freitag, Pradipta Bandyopadhyay, Jan H. Jensen, Visvaldas Kairys, and Walter J. Stevens, "The Effective Fragment Potential Method: A QM-based Approach to Modeling Environmental Effects in Chemistry," Journal of Physical Chemistry A 2001, 105, 293-307. PDF

2000

26. Lynne C. Remer and Jan H. Jensen, "Towards a General Theory of Hydrogen Bonding: The Short, Strong Hydrogen Bond [HOH···OH]-", Journal of Physical Chemistry A 2000, 104, 9266-9275. PDF

25. Visvaldas Kairys and Jan H. Jensen, "QM/MM Boundaries Across Covalent Bonds: A Frozen LMO Based Approach for the Effective Fragment Potential Method," Journal of Physical Chemistry A 2000, 104, 6656-6665. PDF

24. Mark A. Freitag, Mark S. Gordon, Jan H. Jensen, and Walter J. Stevens "Evaluation of Charge Penetration Between Distributed Multipolar Expansions," Journal of Chemical Physics 2000, 112, 7300-7306. PDF

23. Ryan M. Minikis and Jan H. Jensen, "Towards a General Theory of Hydrogen Bonding: A Study of Hydrogen Bonds Involving H2O and HF", International Journal of Quantum Chemistry 2000, 76, 341-358. Invited contribution to the Klaus Ruedenberg honorary volumes. PDF

22. Mark S. Gordon and Jan H. Jensen, "Perspective on "The Physical Nature of the Chemical Bond" Ruedenberg K (1962) Rev Mod Phys 34: 326-376", Theoretical Chemistry Accounts 2000, 103, 248-251.

1999

21. Visvaldas Kairys and Jan H. Jensen, "Evaluation of the Charge Penetration Energy Between Non-Orthogonal Molecular Orbitals Using the Spherical Gaussian Overlap Approximation," Chemical Physics Letters 1999, 315, 140-144. PDF

 

Graduate and Postdoctoral Work

20. Mark S. Gordon and Jan H. Jensen, "Wavefunctions and Chemical Bonding: Interpretation", Encyclopedia of Computational Chemistry, Wiley, 1998, pages 3198-3214. Selected for publication in Handbook of Molecular Physics and Quantum Chemistry, 2003.

19. Josemon Jacob, James H. Espenson, Jan H. Jensen, and Mark S. Gordon, "1,3-Transposition of Allylic Alcohols Catalyzed by Methylrhenium Trioxide", Organometallics, 1998, volume 17, pages 1835-1840.

18. Jan H. Jensen and Mark S. Gordon, "An Approximate Formula for the Intermolecular Pauli Repulsion Between Closed Shell Molecules II. Application to the Effective Fragment Potential Method", Journal of Chemical Physics, 1998, volume 108, pages 4772-4782.

17. Jan H. Jensen and Mark S. Gordon, "An Approximate Formula for the Intermolecular Pauli Repulsion Between Closed Shell Molecules", Molecular Physics, 1996, volume 89, pages 1313-1325.

16. Mark S. Gordon and Jan H. Jensen, "Understanding the Hydrogen Bond Using Quantum Chemistry", Accounts of Chemical Research, 1996, volume 29, pages 536-543.

15. Paul N. Day, Jan H. Jensen, Mark. S. Gordon, Simon P. Webb, Walter J. Stevens, David R. Garmer, Harold Basch, and Drora Cohen, "An Effective Fragment Method for Modeling Solvent Effects in Quantum Mechanical Calculations", Journal of Chemical Physics, 1996, volume 105, pages 1968-1986.

14. Jan H. Jensen, "Modeling Intermolecular Exchange Integrals Between Non-Orthogonal Molecular Orbitals", Journal of Chemical Physics, 1996, volume 104, pages 7795-7796.

13. Jan H. Jensen and Mark S. Gordon, "On the Number of Water Molecules Necessary to Stabilize the Glycine Zwitterion", Journal of the American Chemical Society, 1995, volume 117, pages 8159-8170.

12. Jan H. Jensen and Mark S. Gordon, "Ab Initio Localized Charge Distributions: Theory and a Detailed Analysis of the Water Dimer-Hydrogen Bond", Journal of Physical Chemistry, 1995, volume 99, pages 8091-8107.

11. Kim K. Baldridge, Jan H. Jensen, Nikita Matsunaga, Michael W. Schmidt, Mark S. Gordon, Theresa L. Windus, Jerry A. Boatz, Thomas R. Cundari, "Applications of Parallel GAMESS", ACS Symposium Series 592, American Chemical Society, Washington, D.C., 1995. Chapter 3.

10. George A. Kraus, Jun Li, Mark S. Gordon, and Jan H. Jensen, "Direct Total Syntheses of Frenolicin B and Kalafungin via Highly Regioselective Diels-Alder Reactions", Journal of Organic Chemistry, 1995, volume 60, pages 1154-1159.

9. Jan H. Jensen, Paul N. Day, Mark S. Gordon, Harold Basch, Drora Cohen, David R. Garmer, Morris Kraus, and Walter J. Stevens, "An Effective Fragment Method for Modeling Intermolecular Hydrogen Bonding-Effects on Quantum Mechanical Calculations", In Modeling the Hydrogen Bond, D. A. Smith, Ed. ACS Symposium Series 569, American Chemical Society, Washington, D.C., 1994. Chapter 9.

8. George A. Kraus, Jun Li, Mark S. Gordon, and Jan H. Jensen, "Regiocontrol by Remote Substituents. A Direct Total Synthesis of Racemic Hongconin", Journal of Organic Chemistry, 1994, volume 59, pages 2219-2222.

7. Jan H. Jensen, Keiji Morokuma, and Mark S. Gordon, "The Decomposition of Ethylene: A Theoretical Study", Journal of Chemical Physics, 1994, volume 100, pages 1981-1987.

6. Michael W. Schmidt, Kim K. Baldridge, Jerry A. Boatz, Steven T. Elbert, Mark S. Gordon, Jan H. Jensen, Shiro Koseki, Nikita Matsunaga, Kiet A. Nguyen, Shujun Su, Theresa L. Windus, Michel Dupuis, and John A. Montgomery, "The General Atomic and Molecular Electronic Structure System", Journal of Computational Chemistry, 1993, volume 14, pages 1347-1363.

5. George A. Kraus, Jun Li, Mark S. Gordon, and Jan H. Jensen, "Regiocontrol by Remote Substituents. An Enantioselective Total Synthesis of Frenolicin B via a Highly Regioselective Diels-Alder Reaction", Journal of the American Chemical Society, 1993, volume 115, pages 5859-5860.

4. Jan H. Jensen, Kim K. Baldridge, and Mark S. Gordon, "The Uncatalyzed Peptide Bond Formation in the Gas Phase", Journal of Physical Chemistry, 1992, volume 96, pages 8340-8351.

3. Jan H. Jensen and Mark S. Gordon, "The Conformational Potential Energy Surface of Glycine: A Theoretical Study", Journal of the American Chemical Society, 1991, volume 113, pages 7917-7924.

2. Mark S. Gordon, Marshall T. Carroll, Jan H. Jensen, Larry P. Davis, Larry W. Burggraf and R. Martin Guidry, "The Nature of the Si-N Bond in Silatranes", Organometallics, 1991, volume 10, pages 2657-2660.

1. Jan H. Jensen and Mark S. Gordon, "Splicing I: Using Mixed Basis Sets in Ab Initio Calculations", Journal of Computational Chemistry, 1991, volume 12, pages 421-426.