Tuesday, April 7, 2020

NMRlipids VI: Polarizable force fields

The primary goal of the NMRlipids Project is to find atomic resolution MD simulation force fields that correctly capture the lipid headgroup structures of biologically relevant lipids, and their interactions with ions and other biomolecules.

Current results from the NMRlipids Project indicate that none of the existing force fields correctly captures the lipid headgroup structures (NMRlipids I and IVa). However, the differences between PC, PE, PG and PS headgroup structures are roughly reproduced in CHARMM36, and the description of ion binding to PC and PS headgroups is substantially improved when electronic polarizability is implicitly included using the electronic continuum correction (ECC).

So far, the NMRlipids Project has focused on force fields that lack electronic polarizability. However, the number of available polarizable lipid force fields is increasing, and our PC and PS simulations with ECC suggest that the electronic polarizability may be an essential player in lipid–ion interactions. For these reasons, Batuhan Kav, an active NMRlipids contributor, has suggested the NMRlipids community to make a systematic review and benchmark study of the available polarizable lipid force fields. To this end, we hereby launch the NMRlipids VI project. It will follow the normal NMRlipids rules, with the exception that Batuhan Kav will mainly push the project and thus be the corresponding author.

Note that besides its primary goal, the NMRlipids Project has produced the largest publicly available collection of lipid bilayer MD simulations (indexed also at www.nmrlipids.fi) and evaluations of lipid headgroup force field quality against NMR experiments. To strengthen this side of NMRlipids, we will in NMRlipids VI test a new data contribution, indexing and analysis protocol that paves the way toward the planned leap to the NMRlipids Databank.

As in all NMRlipids projects, the contributions to NMRlipids VI can be made by commenting blog posts related to this topic or by contributing to the related GitHub repository. The GitHub repository already contains a draft review by Batuhan Kav on the published simulations on polarizable lipid force fields. In addition, a python script and stepwise instructions on how to contribute data are available.

In the published literature on polarizable force fields (see Batuhan's draft review), the acyl chains have already been evaluated against NMR order parameter data, but the quality of headgroup structures and ion binding remains largely untested. As a first step to do this test, we need trajectories from polarizable lipid bilayer simulations. During initial attempts to run lipid bilayer simulations with polarizable force fields, it turned out to be significantly more complicated than for non-polarizable force fields. Therefore, we specifically ask contributions from people, who already have data from lipid bilayer simulations with polarizable force fields, or know how to run these in practise. The polarizable lipid force fields that we are aware of are:
If you have access to lipid bilayer simulations using these or other polarizable lipid force fields, and are willing to contribute to the project, please contact us and/or contribute the data according to the instructions. Currently our analysis script works for data from Gromacs and NAMD, but our goal is to accept data from any MD engine. Do not hesitate to give us feedback on the data contribution and analysis, or to develop it further by yourself on GitHub.

Batuhan Kav
Markus Miettinen
Samuli Ollila