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Intermolecular Interactions and the Role of Dynamics for Chemical Reactions in Complex Systems

English title Intermolecular Interactions and the Role of Dynamics for Chemical Reactions in Complex Systems
Applicant Meuwly Markus
Number 149439
Funding scheme Project funding
Research institution Physikalische Chemie Departement Chemie Universität Basel
Institution of higher education University of Basel - BS
Main discipline Physical Chemistry
Start/End 01.10.2013 - 30.09.2016
Approved amount 430'000.00
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Keywords (7)

Molecular Dynamics; Metal Force Fields; Multipolar Force Fields; Force Fields; Protein-Ligand Interactions; QM/MM Simulations; Reactive Dynamics

Lay Summary (German)

Lead
Das Projekt beschäftigt sich mit der Untersuchung von chemischen Reaktionen. Von besonderer praktischer Bedeutung sind dabei Reaktionen, an denen Metalle - wie Eisen oder Kupfer - beteiligt sind. Dies insbesondere deshalb, weil solche Metallzentren auch in biologischen Molekülen - also Proteinen - wesentliche Funktionen übernehmen, wie beispielsweise den Sauerstofftransport im Blut.
Lay summary

Im Allgemeinen ist eine chemische Reaktion durch die Rate charakterisiert. Die Reaktionsrate gibt darüber Auskunft, wie schnell ein Prozess abläuft. Je schneller und einfacher der Prozess ist, desto weniger Energie muss aufgewendet werden, um das gewünschte Produkt zu erhalten. Typische chemische Reaktionen laufen in Sekunden ab. Proteine können eine Reaktionsgeschwindigkeit um viele Grössenordnungen beschleunigen. Weil bei der experimentellen Charakterisierung oft Zwischenzustände besetzt werden - die Reaktion läuft also oft nicht direkt zwischen Ausgangs- und Endsubstanz ab, sondern durch sogenannte Intermediate - ist deren Charakterisierung sehr schwierig. Zudem sind die atomaren Prozesse oft nicht direkt beobachtbar. Unter solchen Umständen sind Computersimulationen ein enorm hilfreiches Instrument.

Die genausten Rechnungen sind heutzutage quantenchemische Rechnungen. Für Systeme, bei denen Metalle eine Rolle spielen, ist die typische Rechenzeit für eine Energie in der Grössenordnung von Minuten bis Stunden - je nach Systemgrösse und Coputerarchitektur. Um die Dynamik eines reaktiven Prozesses zu verfolgen, sind in der Grössenordnung von mindestens 10^8 solcher Rechnungen durchzuführen, was selbst von den schnellsten Rechnern nicht mehr bewältigt werden kann.

Das Projekt hat es sich zum Ziel gesetzt, die Rechenzeit dramatisch zu beschleunigen. Dies geschieht durch den Einsatz von empirischen Kraftfeldern, welche ein Modell für die zwischenmolekularen Wechselwirkungen sind. Kraftfelder können sukzessive verbessert werden, sodass quantitative Rechnungen damit durchgeführt werden können. Ein wesentliches Ziel der Arbeiten ist es, die Bedeutung atomarer Bewegungen für den Ablauf und die Rate von chemischen Reaktionen zu klären. Damit ist man im besten Fall in der Lage, Vorschläge für gezielte Veränderungen an den reagierenden Spezies vorzuschlagen, welche zu einer Beschleunigung der Reaktion führen.

Direct link to Lay Summary Last update: 03.10.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
A Toolkit to Fit Nonbonded Parameters from and for Condensed Phase Simulations
Hedin Florent, El Hage Krystel, Meuwly Markus (2016), A Toolkit to Fit Nonbonded Parameters from and for Condensed Phase Simulations, in JCIM, 56(8), 1479-1489.
Computational Approaches for Studying Enzyme Mechanism
(2016), Computational Approaches for Studying Enzyme Mechanism, Academic Press, NY.
Copper Oxidation/Reduction in Water and Protein: Studies with DFTB3/MM and VALBOND Molecular Dynamics Simulations
Jin Haiyun, Goyal Puja, Das Akshaya Kumar, Gaus Michael, Meuwly Markus, Cui Qiang (2016), Copper Oxidation/Reduction in Water and Protein: Studies with DFTB3/MM and VALBOND Molecular Dynamics Simulations, in JPCB, 120(8), 1894-1910.
Empirical Force Fields for Mechanistic Studies of Chemical Reactions in Proteins
Das A. K., Meuwly M. (2016), Empirical Force Fields for Mechanistic Studies of Chemical Reactions in Proteins, in Voth GA (ed.), Springer, NY, 31-55.
Impact of Quadrupolar Electrostatics on Atoms Adjacent to the Sigma-Hole in Condensed-Phase Simulations
El Hage Krystel, Bereau Tristan, Jakobsen Sofie, Meuwly Markus (2016), Impact of Quadrupolar Electrostatics on Atoms Adjacent to the Sigma-Hole in Condensed-Phase Simulations, in JCTC, 12(7), 3008-3019.
Inner-Shell Water Rearrangement Following Photoexcitation of Tris(2,2 `-bipyridine)iron(II)
Das Akshaya K., Solomon R. V., Hofmann Franziska, Meuwly Markus (2016), Inner-Shell Water Rearrangement Following Photoexcitation of Tris(2,2 `-bipyridine)iron(II), in JPCB, 120(1), 206-216.
Ligand and interfacial dynamics in a homodimeric hemoglobin
Gupta Prashant Kumar, Meuwly Markus (2016), Ligand and interfacial dynamics in a homodimeric hemoglobin, in Struct. Dyn., 3(1), 012003.
Spectroscopy and dynamics of double proton transfer in formic acid dimer
Mackeprang Kasper, Xu Zhen-Hao, Maroun Zeina, Meuwly Markus, Kjaergaard Henrik G. (2016), Spectroscopy and dynamics of double proton transfer in formic acid dimer, in PCCP, 18(35), 24654-24662.
Structural Interpretation of Metastable States in Myoglobin-NO
Soloviov Maksym, Das Akshaya K., Meuwly Markus (2016), Structural Interpretation of Metastable States in Myoglobin-NO, in Angewandte, 55(34), 10126-10130.
A comparative analysis of clustering algorithms: O-2 migration in truncated hemoglobin I from transition networks
Cazade Pierre-Andre, Zheng Wenwei, Prada-Gracia Diego, Berezovska Ganna, Rao Francesco, Clementi Cecilia, Meuwly Markus (2015), A comparative analysis of clustering algorithms: O-2 migration in truncated hemoglobin I from transition networks, in JCP, 142(2), 025103.
Coupled protein-ligand dynamics in truncated hemoglobin N from atomistic simulations and transition networks
Cazade Pierre-Andre, Berezovska Ganna, Meuwly Markus (2015), Coupled protein-ligand dynamics in truncated hemoglobin N from atomistic simulations and transition networks, in BBA, 1850(5, SI), 996-1005.
Multipolar Force Fields and Their Effects on Solvent Dynamics around Simple Solutes
Jakobsen Sofie, Bereau Tristan, Meuwly Markus (2015), Multipolar Force Fields and Their Effects on Solvent Dynamics around Simple Solutes, in JPCB, 119(7), 3034-3045.
Reproducing kernel potential energy surfaces in biomolecular simulations: Nitric oxide binding to myoglobin
Soloviov Maksym, Meuwly Markus (2015), Reproducing kernel potential energy surfaces in biomolecular simulations: Nitric oxide binding to myoglobin, in JCP, 143(10), 105103.
Solvation of fluoro-acetonitrile in water by 2D-IR spectroscopy: A combined experimental-computational study
Cazade Pierre-Andre, Tran Halina, Bereau Tristan, Das Akshaya K., Klaesi Felix, Hamm Peter, Meuwly Markus (2015), Solvation of fluoro-acetonitrile in water by 2D-IR spectroscopy: A combined experimental-computational study, in JCP, 142(21), 212415.
Vibrational Relaxation and Energy Migration of N-Methylacetamide in Water: The Role of Non bonded Interactions
Cazade Pierre-Andre, Hedin Florent, Xu Zhen-Hao, Meuwly Markus (2015), Vibrational Relaxation and Energy Migration of N-Methylacetamide in Water: The Role of Non bonded Interactions, in JCP, 119(7), 3112-3122.
CO-dynamics in the active site of cytochrome c oxidase
Soloviov Maksym, Meuwly Markus (2014), CO-dynamics in the active site of cytochrome c oxidase, in JCP, 140(14), 145101.
Computational Two-Dimensional Infrared Spectroscopy without Maps: N-Methylacetamide in Water
Cazade Pierre-Andre, Bereau Tristan, Meuwly Markus (2014), Computational Two-Dimensional Infrared Spectroscopy without Maps: N-Methylacetamide in Water, in JPCB, 118(28), 8135-8147.

Collaboration

Group / person Country
Types of collaboration
Prof. P. Hamm, University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. G. U. Nienhaus, Institute of Physics and KIT Karlsruhe Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Q. Cui, University of Madison/WI United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Meeting on EVB-Simulations, Talk given at a conference Small Ligands to Probe Protein Interiors: Ligand Dynamics, Metastable States, and Spectroscopy in Heme- Containing Proteins 05.06.2016 Uppsala, Sweden Meuwly Markus;
Shanghai Symposium on Frontiers of Computational Chemistry Talk given at a conference Applied Atomistic Simulations 20.08.2015 Shanghai, China Meuwly Markus;
CHARMM MEeting Talk given at a conference Reproducing Kernel-based potentials in CHARMM ∗ 01.07.2015 Wien, Austria Meuwly Markus; Soloviov Maksym;
Photodynamics Meeting, Oaxaca Talk given at a conference Electronically Induced Dynamics from Atomistic Simulations 20.10.2014 Oaxaca, Mexico Meuwly Markus; Das Akshaya Kumar;
Telluride Workshop on “Proton Transfer” Talk given at a conference Force Field Methods for Investigating Proton Transfer in Complex Environments ∗ 01.07.2014 Telluride, United States of America Xu Zhen-Hao; Meuwly Markus;
Telluride Workshop on “Many-Body Interactions”, Talk given at a conference Atomistic Simulations with Multipoles: Case Studies from Spectroscopy and Chemical Dynamics 01.06.2014 Telluride, United States of America Meuwly Markus; Bereau Tristan;


Associated projects

Number Title Start Funding scheme
132406 Intermolecular Interactions and the Role of Dynamics for Chemical Reactions in Complex Systems 01.10.2010 Project funding
125760 NCCR MUST: Molecular Ultrafast Science and Technology (phase I) 01.07.2010 National Centres of Competence in Research (NCCRs)
169079 Intermolecular Interactions and the Role of Dynamics for Chemical Reactions in Complex Systems 01.10.2016 Project funding
132406 Intermolecular Interactions and the Role of Dynamics for Chemical Reactions in Complex Systems 01.10.2010 Project funding

Abstract

The overall goal of this project is to develop numerical methods andcomputational strategies to characterize, understand and eventuallypredict the energetics and dynamics of chemical reactions in complexenvironments and to apply them to chemically and biologically relevantsystems. To this end, a combination of reactive molecular dynamics andphysics-based/tailored force fields is employed to investigateprocesses including ligand-transport, ligand-binding and elementarysteps in metal-catalyzed reactions. At the methodological level, wewill implement energy-based switching in adiabatic reactive moleculardynamics (ARMD) to allow microcanonical sampling for small systems andcombine ARMD with VALBOND and VALBOND-TRANS to treat reactionsinvolving metal-containing complexes. Furthermore, distributedmultipoles (MTPs) based on local reference axis systems for MDsimulations of larger, pharmacologically relevant molecules will beimplemented. Many metal-based complexes in catalysis contain organicring-compounds which constitute important functional units and need tobe described with accurate force fields such as multipolarelectrostatics. These developments are applied to NO and N2Odiffusion in native and engineered Fe- and Cu-containing proteins. Toclarify the mode-of-action of metal-based catalysts, specifically aRu-catalyst suitable for converting methanol to molecular hydrogen,docking and crystallographic studies with host proteins includinglysozyme, ribonuclease A and ketosteroid isomerase will beundertaken. Furthermore, the combination of ARMD with VALBOND-TRANSwill be used to characterize individual reactive steps ofIr(III)-complexes involved in homogeneous water oxidation. For all thestudies involving Cu-, Ru- or Ir-containing species force fieldparametrizations based on VALBOND and MTPs will be developed based onexperimental and in silico data.
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