Functional regulation of aquaporin dynamics by lipid bilayer composition

With the diversity of lipid-protein interactions, any observed membrane protein dynamics or functions directly depend on the lipid bilayer selection. However, the implications of lipid bilayer choice are seldom considered unless characteristic lipid-protein interactions have been previously reported. Using molecular dynamics simulation, we characterize the effects of membrane embedding on plant aquaporin SoPIP2;1, which has no reported high-affinity lipid interactions. The regulatory impacts of a realistic lipid bilayer, and nine different homogeneous bilayers, on varying SoPIP2;1 dynamics were examined. We demonstrate that SoPIP2;1's structure, thermodynamics, kinetics, and water transport are altered as a function of each membrane construct's ensemble properties. Notably, the realistic bilayer provides stabilization of non-functional SoPIP2;1 metastable states. Hydrophobic mismatch and lipid order parameter calculations further explain how lipid ensemble proprties manipulate SoPIP2;1 ..., Molecular dynamics trajectories were generated using AMBER18 software on a local computational cluster. Resulting analysis files were created via python scripts and/or java-based software (i.e. Membrainy). For more information about specific codes, please refer to our Github Repository: https://github.com/ShuklaGroup/Lipid_composition_on_AQP/ 
This work has been performed by Anh T. P. Nguyen, Austin T. Weigle & Diwakar Shukla at the University of Illinois Urbana-Champaign.
This Dryad dataset has been made available in compliance with the \"minimum dataset\" requirement per the Data Availability guidelines by Nature Communications.
For further inquiries concerning further data availability (i.e., 29 TB of molecular dynamics trajectories), please contact Prof. Diwakar Shukla at [e-mail] . Austin T. Weigle (https://orcid.org/0000-0002-1619-2452) prepared this Dryad repository., , # Functional regulation of aquaporin dynamics by lipid bilayer composition

Our data can be separated into a few different categories, whose architecture we further dissect below.

00 - Molecular dynamics simulations must be performed using topologies (*.parm7/*.prmtop) and coordinate (*.rst/*.ncrst) files. We have provided AMBER-compatible simulation files parameterized using the CHARMM36 force fields.
01 - Our primary method of choice for this manuscript was via an adaptive sampling regime, where the resulting aggregate trajectories were incorporated into master kinetic frameworks using Markov state models (MSMs). A MSM has been made and optimized for each SoPIP2:lipid bilayer construct. To make an MSM, one generally follows a generalized protocol:
-> Featurization - numerical ways to describe the structures obtained in molecular dynamics trajectories in \"n\" degrees of
freedom using reaction coordinates. Reaction coordinates are chosen as described in our Methods
section to best...