TY - JOUR
T1 - Obtaining Protein Association Energy Landscape for Integral Membrane Proteins
AU - Rajagopal, Nandhini
AU - Nangia, Shikha
N1 - Funding Information:
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jctc.9b00626 . Description of PANEL python scripts; details of PANEL parameters; parameters used for generating PANEL for each system; list of pairwise LJ and Columbic interaction energies; performance analysis; radial distance distribution; rotational angle conventions; convergence tests, minimum energy PANEL plots; reverse mapped atomistic structures; low energy region descriptions; and OmpF wt and mutated dimer PANEL landscapes ( PDF ) This work is supported by the CAREER CBET-1453312 grant from the National Science Foundation. Computational resources were provided by the Information and Technology Services at Syracuse University (Eric Sedore, Larne Pekowsky, and Michael R. Brady) as well as by the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number ACI-1053575. The authors declare no competing financial interest.
Funding Information:
This work is supported by the CAREER CBET-1453312 grant from the National Science Foundation. Computational resources were provided by the Information and Technology Services at Syracuse University (Eric Sedore, Larne Pekowsky, and Michael R. Brady) as well as by the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number ACI-1053575.
Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/11/12
Y1 - 2019/11/12
N2 - Integral membrane proteins are ubiquitous in biological cellular and subcellular membranes. Despite their significance to cell function, isolation of membrane proteins from their hydrophobic lipid environment and further characterization remains a challenge. To obtain insights into membrane proteins, computational approaches such as docking or self-assembly simulations have been used; however, the promise of these approaches has been limited due to the computational cost. Here we present a new approach called Protein AssociatioN Energy Landscape (PANEL) that provides an extensive and converged data set for all possible conformations of membrane protein associations using a combination of stochastic sampling and equilibration simulations. The PANEL method samples the rotational space around both interacting proteins to obtain the comprehensive interaction energy landscape. We demonstrate the versatility of the PANEL method using two distinct applications: (a) dimerization of claudin-5 tight junction proteins in phospholipid bilayer membrane and (b) dimer and trimer formation of the Outer membrane protein F (OmpF) in the lipopolysaccharide-rich bacterial outer membrane. Both applications required only a fraction of simulation cost compared to self-assembly simulations. The method is robust as it can capture changes in protein-protein conformations caused by point mutations. Moreover, the method is versatile and independent of the molecular resolution (atomistic or coarse grain) or the choice of force field employed to compute the pair-interaction energies. The PANEL method is implemented in easy-to-use scripts that are available for download for general use by the scientific community to characterize any pair of interacting integral membrane proteins.
AB - Integral membrane proteins are ubiquitous in biological cellular and subcellular membranes. Despite their significance to cell function, isolation of membrane proteins from their hydrophobic lipid environment and further characterization remains a challenge. To obtain insights into membrane proteins, computational approaches such as docking or self-assembly simulations have been used; however, the promise of these approaches has been limited due to the computational cost. Here we present a new approach called Protein AssociatioN Energy Landscape (PANEL) that provides an extensive and converged data set for all possible conformations of membrane protein associations using a combination of stochastic sampling and equilibration simulations. The PANEL method samples the rotational space around both interacting proteins to obtain the comprehensive interaction energy landscape. We demonstrate the versatility of the PANEL method using two distinct applications: (a) dimerization of claudin-5 tight junction proteins in phospholipid bilayer membrane and (b) dimer and trimer formation of the Outer membrane protein F (OmpF) in the lipopolysaccharide-rich bacterial outer membrane. Both applications required only a fraction of simulation cost compared to self-assembly simulations. The method is robust as it can capture changes in protein-protein conformations caused by point mutations. Moreover, the method is versatile and independent of the molecular resolution (atomistic or coarse grain) or the choice of force field employed to compute the pair-interaction energies. The PANEL method is implemented in easy-to-use scripts that are available for download for general use by the scientific community to characterize any pair of interacting integral membrane proteins.
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U2 - 10.1021/acs.jctc.9b00626
DO - 10.1021/acs.jctc.9b00626
M3 - Article
C2 - 31593632
AN - SCOPUS:85074286286
SN - 1549-9618
VL - 15
SP - 6444
EP - 6455
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
IS - 11
ER -