%0 Conference Paper
%A Bondar, Ana-Nicoleta
%A Hristova, Kalina
%A Wimley, William C.
%T Mechanism by which water interactions stabilize a pH-dependent membrane pore
%@ 0006-3495
%M FZJ-2024-02760
%D 2024
%X Peptides that can form large, stable pores at acidic pH values are of direct interest to deliver cargo to cells and cell compartments with acidic pH. Peptides of the pHD (pH-dependent delivery peptides) have the unique property of forming stable pores with diameters of ∼30–-100 Å at pH below ∼6. Such a pore size could be established with ∼8–30 peptides, and each peptide carries several sidechains that can titrate at the pH of interest. Understanding which protonation states are compatible with stable pore formation is essential, as it could guide rational design of new peptides with pore-forming properties tailored to specific cells and cell compartments. We report on experiment-guided atomistic simulations that probe the protonation-coupled structure and dynamics of pHD pores. To identify interactions that could contribute to the stability of the pores, we used the Bridge/Bridge2 graph algorithm and graphical user interface to compute the hydrogen-bond networks sampled by the peptides, lipid phosphate groups, and water. We identify a complex network of interactions between peptides, lipid headgroups, and water molecules, with water molecules bridging neighboring peptides via dynamic hydrogen bonding. Research was supported in part by the National Institutes of Health award no. 1R01GM151326-01 and by the computing time allocation PHDPORES from the JURECA-DC Supercomputing Cluster of the Forschungszentrum Jülich.
%B Biophysical Society Meeting
%C 10 Feb 2024 - 14 Feb 2024, Philadelphia (USA)
Y2 10 Feb 2024 - 14 Feb 2024
M2 Philadelphia, USA
%F PUB:(DE-HGF)1
%9 Abstract
%R 10.1016/j.bpj.2023.11.2011
%U https://juser.fz-juelich.de/record/1025183