Joint Physics Dept-MtSE Seminar

March 14th, Thursday (*SPECIAL DAY*)

Atomic Resolution through Simulations? Rethinking Biomolecular Model Development

Dr. Markus Miettinen

Max Planck Institute of Colloids and Interfaces

(Biophysics, Host: Dias)

*SPECIAL TIME: 11:15 am - 12:15 pm with 11 am tea time

*SPECIAL ROOM: Tiernan 408

Today, molecular dynamics (MD) simulations allow systems spanning tens of nanometers to be followed up to milliseconds at atomic/femtosecond resolution. As this is the spatiotemporal regime where many biologically relevant molecular processes take place, MD holds promise for resolving in unprecedented detail the biologically relevant conformations and dynamics of biomolecules.

Here I first demonstrate that current MD does not provide the sharp Ångström-resolution picture it could, at least not for phospholipid bilayers. This finding was borne out of the open scientific collaboration NMRlipids, where we use the sensitive and robust C-H order parameters from nuclear magnetic resonance spectroscopy (NMR) to assess the quality of lipid headgroup, glycerol backbone and acyl chain conformations in different MD models (also known as force fields). [1-4]

I then argue that by improving the force fields one could considerably sharpen the image that MD provides on biomolecular systems. To speed up the evolution of force fields, I propose 1) adopting the open collaboration approaches already successfully used by the open source code development community (cf. Linux kernel development), and 2) defining a set of quantitative structural constraints obtained from sensitive experiments (NMR, scattering) as the development target.

[1] http://nmrlipids.blogspot.fi

[2] Botan et al. J. Phys. Chem. B 119 15075 (2015) [http://dx.doi.org/10.1021/acs.jpcb.5b04878]

[3] Catte et al. Phys. Chem. Chem. Phys. 18 32560 (2016) [http://dx.doi.org/10.1039/C6CP04883H]

[4]https://github.com/NMRLipids/NMRlipidsIVotherHGs/blob/master/Manuscript/manuscriptPS.pdf