QM/MM Car-Parrinello Simulations of Biological Systems
Ab initio molecular dynamics simulations based on density functional theory
have become a powerful tool in the study of physical and chemical systems.
Applications to biological problems have started only very recently and are
still in their infancy. Using parallel computers, systems of a few 100-1000
of atoms can be routinely investigated. By extending the method to a mixed
quantum-classical (QM/MM) hybrid scheme, the part of the system that is taken
explicitly into account can be enlarged further. Such an approach is especially
attractive for the in situ investigation of biochemical reactions in which
the reactive site of the system can be treated at the quantum mechanical level
whereas the effects of the protein environment are taken into account within
an empirical force field description.
Current projects:
(i)Test Case Systems: Small Peptides and Nucleotides in Solution
(ii) Ab initio Modelling of Enzymes
(iii) Rational Design of Radiopharmaceuticals
(iv) Prion Proteins
(v) DNA and RNA
(vi) Photoreceptors
Publications:
- S. Piana and U. Rothlisberger
Folding Pathways for Initiator and Effector Procaspases from Computer
Simulations
(accepted in Proteins)
- M. Cascella, C. Micheletti, U. Rothlisberger, and P. Carloni
Evolutionary-Conserved Functional Mechanics across Pepsins and Retropepsins
(submitted to J. Am. Chem. Soc.)
- U. Röhrig, L. Guidoni, and U. Rothlisberger
Structure and Dynamics of the Rhodopsin Chromophore
(preprint)
- P. Maurer, and U. Rothlisberger
Molecular Dynamics Simulations of Human Hexokinase I
(preprint)
- U. Röhrig, L. Guidoni, A.Laio, I. Frank, and U. Rothlisberger
A Molecular Spring for Vision
J. Am. Chem. Soc. (ASAP article)
- M. Dal Peraro, L.I. Llarlull, A. Vila, U. Rothlisberger, and P. Carloni
Water-Assisted Reaction Mechanism of Mono Zinc-Lactamases
J. Am. Chem. Soc. 126, 12661-12668 (2004)
- L. Guidoni, K. Spiegel, M. Zumstein, and U. Rothlisberger
Green Oxidation Catalysts: Computational Design of High Efficiency Models
of Galactose Oxidase
Angew. Chem. 116, 3348-3351 (2004)
- H. Hugosson, K. Spiegel, P. Carloni and U. Rothlisberger
A Comparative Theoretical Study of DNA and RNA Nucleotide Solvation
in Water
(manuscript in preparation)
- H. Hugosson, A. Laio, P. Maurer, and U. Rothlisberger
A Comparative Theoretical Study of Dipeptide Solvation in Water
(submitted to J. Phys. Chem. B)
- K. Spiegel, U. Rothlisberger, and P. Carloni
Cisplatin Binding to DNA Oligomers from Hybrid Car-Parrinello Molecular
Dynamics Simulations
J. Phys. Chem. B 108, 2699-2707 (2004)
- S. Piana, D. Bucher, P. Carloni, and U. Rothlisberger
Reaction Mechanism of HIV-1 Protease by Hybrid Car-Parrinello MD/Classical
MD Simulations
J. Phys. Chem. B 108, 11139-11149 (2004)
- Klein, R. Schiffmann, G. Folkers, S. Piana, and U. Rothlisberger
Protonation States of Methionine Aminopeptidase and their Relevance
for Inhibitor Binding and Catalytic Activity
J. Biol.Chem. 278, 47862-47867 (2003)
- S. Piana and U. Rothlisberger
Molecular Dynamics Simulations of Structural Changes During Procaspase-3
Activation
Proteins 55, 932-941 (2004)
- S. Piana, M. Sulpizi, and U. Rothlisberger
Structure-based thermodynamic analysis of caspases reveals key residues
for dimerization and activity
Biochemistry 42, 7820-7828 (2003)
- A. Magistrato, W.F. DeGrado, U. Rothlisberger, and M.L. Klein
Structural and Dynamical Characterization of Dizinc DF1, a Biomimetic
Compound of Diiron Proteins via ab initio and Hybrid (QM/MM) Molecular
Dynamics
J.Phys. Chem. B 107, 4182-4188 (2003)
- M. Sulpizi, U. Rothlisberger, and P. Carloni
Molecular Dynamics Studies of Caspase-3 Dimer
Biophys. J. 84, 2207-2215 (2003)
- M. Sulpizi, A. Laio, J. VandeVondele, U. Rothlisberger, A. Cattaneo and
P. Carloni
Reaction Mechanism of Caspases: Insights from Mixed QM/MM Car-Parrinello
Simulations
Proteins- Structure, Function and Genetics 52, 212-224 (2003)
- U. Röhrig, L. Guidoni, and U. Rothlisberger
Early Steps of the Intramolecular Signal Transduction in Rhodopsin
Explored by Molecular Dynamics Simulations
Biochemistry 41, 10799-10809 (2002)
- M. Colombo, L. Guidoni, A. Laio, A. Magistrato, P. Maurer, S. Piana, U.
Röhrig, K. Spiegel, M. Sulpizi, J. VandeVondele, M. Zumstein, and U.
Rothlisberger
Hybrid QM/MM Car-Parrinello Simulations of Catalytic and Enzymatic Reactions
CHIMIA 56, 11-17 (2002)
- P. Carloni, U. Rothlisberger, and M. Parrinello
The Role and Perspective of Ab-initio Molecular Dynamics in the Study
of Biological Systems
Acc. Chem. Res. 35, 455-464 (2002)
- S. Piana, P. Carloni and U. Rothlisberger
Flexibility-Assisted Catalysis: Molecular Mechanisms of Compensatory
Mutations in HIV-1 PR
Protein Sci. 11, 1393-2402 (2002)
- P. Carloni and U. Rothlisberger
Simulations of Enzymatic Systems: Perspectives from Car-Parrinello
Molecular Dynamics Simulations
"˜Theoretical Biochemistry - Processes and Properties of Biological
Systems", L. Eriksson (Ed.), Elsevier Science p. 215 (2001)
- U. Rothlisberger, P. Carloni, K. Doclo and M. Parrinello
A Comparative Study of Galactose Oxidase and Active Site Analogs Based
on QM/MM Car-Parrinello Simulations
J. Biol. Inorg. Chem. 5, 236 (2000)
- U. Rothlisberger and P. Carloni
Ab Initio Molecular Dynamics Studies of a Synthetic Biomimetic Model
of Galactose Oxidase
Intl. J.Quant.Chem. 73, 209 (1999)
- U. Rothlisberger
Ab initio and Hybrid Molecular Dynamics Simulations of the Active Site
of Human Carbonic Anhydrase II: A Test Case Study
ACS Symp. Ser. 712, J. Gao and M.A. Thompson (eds), 'Combined Quantum Mechanical
and Molecular Mechanical Methods', Am. Chem. Soc., Washington DC (1998),
p.264
