link to homepage

Institute for Advanced Simulations (IAS)

Navigation and service

Seminar by Dr. Davide Branduardi

Crucell Vaccine Institute, Leiden (The Netherlands)

11.Jun.2014 11:00
11.Jun.2014 12:00
Lecture room 2009, Jülich GRS building (16.15)

Sampling reactive paths with biased dynamics: ATP-Mg2+ conformational transitions

Very often the prediction of the long-time dynamics of a system requires the calculation of the free-energy landscape of the process of interest. This can be generally obtained with straightforward sampling or with enhanced-sampling methods like umbrella sampling [1]. Nevertheless the interpretation of the results from such methods may be strongly affected from artefacts that are connected with the choice of the collective variables.

Here I applied String method [2], which is a strategy that aims to find the best one-dimensional free-energy profile derived from a highly-dimensional descriptor space and I adopt the Cartesian coordinates as collective variables. This space is the most intuitive and complete descriptor which, due to some peculiar properties, provides a distortion-free free-energy landscape. However its use in practice is affected by its
non roto-translational invariance.

Here I introduce a novel flavour of roto-translational invariant string method in Cartesian space [3] which solves this issue and I show its application in the case of alanine dipeptide in vacuum and adenosine-5'-triphosphate (ATP) complexed with Mg2+ ion in water.
I investigate the main conformational barriers, analyse the committor probability and perform free-energy decomposition. Interestingly microsolvation plays a key role that cannot be captured with traditional coordination parameters.

Additionally, since this approach introduces a projection which is restricted to the minimum free energy path only, the effect of the entropy orthogonal to the path is recovered by using well-tempered metadynamics[4] in path collective variables[5] and it show that this adds a further level of understanding of the problem which shows the importance of integrating different complementary free-energy techniques.

[1] Roux, B. "The calculation of the potential of mean force using computer simulations" (1995), Comp. Phys. Comm., 91, 275-282.
[2] Maragliano, L.; Fischer, A.; Vanden-Eijnden, E.; Ciccotti, G. "String method in collective variables: minimum free energy paths and isocommittor surfaces" (2006), J. Chem. Phys., 125(2), 024106.
[3] Branduardi, D.; Faraldo-Gomez, J.D. "String method for calculation of minimum free-energy paths in cartesian space in freely tumbling systems" (2013), J. Chem. Theor. Comp., 9(9), 4140-4154.
[4] A Barducci, G Bussi, and M Parrinello. "Well-tempered metadynamics: A smoothly converging and tunable free-energy method" (2008) Phys. Rev. Lett., 100(2), 020603.
[5] Branduardi, D.; Gervasio, F.L.; Parrinello, M "From A to B in free energy space" (2007), J. Chem. Phys., (126), 054103.