Our research interests are concentrated on ab initio MD methods based on density functional theory (Car-Parrinello simulations) and their application, adaption and extension to systems of chemical and/or biological interest, this includes the following research topics:
(i) Development of Hybrid QM/MM Methods for Combined Quantum/Classical Car-Parrinello Simulations.
(ii) Development of Long-Time Scale Techniques for Ab initio MD Simulations.
(iii) In situ Simulations of Chemical Reactions and Photoactive systems in Gas Phase and in Solution.
(iv) Ab initio Simulations of Biological Systems.
Our group has also developed, and is continually developing, a hybrid QM/MM extension to the Car-Parrinello simulations, allowing investigations of larger (more realistic) biological systems. This is done through a partioning of the descripion of the system into a, detailed, QM(quantum mechanic) part and a, less detailed, MM (molecular mechanic) part.
Development of Hybrid QM/MM Methods for Combined Quantum/Classical Car-Parrinello Simulations
|An ideal way of simulating a large realistic system would be to apply a classical description whenever possible and a computationally more demanding ab initio description where necessary. We are working on the combination of density functional (DFT) based first principles simulations with classical MD methods (see also QM/MM). Depending on where the border between quantum and classical parts of the system is drawn, the resulting interface region can be complex and a major part of the work focuses on the development of well defined interface regions in order to connect the two approaches in a rigorous way.|
|Understandably, since QM/MM simulations are one of our groups main interests, there are seveal projects underway to improve and extend the applcability of the QM/MM simulations.|
(i) Driving Chemical Reactions with Charge Constraints.
(ii) Atomatic Procedures for the Generation of DFT Consistent Force Fields.
(iii) Automatic Fitting Procedure for QM/MM Boundary Atoms.
(iv) Particle Exchange Restraints for QM/MM Solvent Systems.
(v) Non-equilibrium dynamics.
(vi) D-RESP: Dynamical Restrained Electrostatic Potential Derived Charges.
(vii) A Hamiltonian Electrostatic Coupling Scheme for Plane Wave Based QM/MM Car-Parrinello Simulations.
Development of Long-Time Scale Techniques for Ab initio MD Simulations
|Ab initio MD simulations are a new and promising tool in the computer simulation of complex chemical reactions. Systems of a few hundred atoms can be treated with this approach. A serious limitation of ab initio MD techniques is however the limited time scale of a few tens of picoseconds. In this short time only a rather limited portion of the potential energy surface can be sampled. This problem is especially severe for the study of chemical reactions in which the system has to overcome a high activation (free) energy. To sample such a rare event, long sampling times are necessary.
|Furthermore, complex enzymatic or organometallic catalysis reactions with bulky ligands can imply very slow conformational changes.To know the relevant configurations of the system, or the relevant portion of phase space where the reaction happens, one needs to know the essential motions the system can do in long time scales.
In this project we investigate different long time scale techniques for ab initio molecular dynamics simulations.
|(i) Non-equilibrium molecular dynamics to sample phase space (ii) Extract information for driving chemically reactive systems directly from their electronic structure. (iii) CAFES: Canonical Adiabatic Free Energy Sampling. (iv) Using a classical biasing potential, based on nuclear positions, to guide systems more efficiently through phase space.|
Study of Chemical Reactions in Gas Phase and in Solution
|Most of the standard methods to treat reaction dynamics are based on a point by point characterization of the potential energy surface(s) (PES) via ab initio or semiempirical quantum chemistry calculations. This is a time consuming procedure even in the case of relatively simple systems; a fact that has so far prevented the study of complex organic and biochemical reactions.
|Ab initio MD simulation where the system itself chooses automatically the relevant portion of the PES offer a new and promising alternative to the standard techniques. We are using this relatively recent method to characterize:|
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.
(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