A Simple and Transferable All-Atom/Coarse-Grained Hybrid Model to Study Membrane Processes

S Genheden and JW Essex, JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 11, 4749-4759 (2015).

DOI: 10.1021/acs.jctc.5b00469

We present an efficient all-atom/coarse-grained hybrid model and apply it to membrane processes. This model is an extension of the all- atom/ELBA model applied previously to processes in water. Here, we improve the efficiency of the model by implementing a multiple-time step integrator that allows the atoms and the coarse-grained beads to be propagated at different timesteps. Furthermore, we fine-tune the interaction between the atoms and the coarse-grained beads by computing the potential of mean force of amino acid side chain analogs along the membrane normal and comparing to atomistic simulations. The model was independently validated on the calculation of small-molecule partition coefficients. Finally, we apply the model to membrane peptides. We studied the tilt angle of the Walp23 and Kalp23 helices in two different model membranes and the stability of the glycophorin A dimer. The model is efficient, accurate, and straightforward to use, as it does not require any extra interaction particles, layers of atomistic solvent molecules or tabulated potentials, thus offering a novel, simple approach to study membrane processes.

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