Modeling of Specific Lipopolysaccharide Binding Sites on a Gram-Negative Porin
Modeling of Specific Lipopolysaccharide Binding Sites on a Gram-Negative Porin
复制标题
革兰氏阴性孔蛋白上特定脂多糖结合位点的建模
DOI：
10.1021/acs.jpcb.9b03669
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Kleinekathöfer, Ulrich
中科院分区：
文献类型：
--
作者：
Kesireddy, Anusha;Pothula, Karunakar R.;Lee, Jumin;Patel, Dhilon S.;Pathania, Monisha;van den Berg, Bert;Im, Wonpil;Kleinekathöfer, Ulrich
Protein-lipopolysaccharide (LPS) interactions play an important role in providing a stable outer membrane to Gram-negative bacteria. However, the LPS molecules are highly viscous, and sampling LPS motions is thus challenging on a microsecond time scale in simulations. To this end, we introduce a new protocol to randomly allow the LPS molecules to self-assemble around the protein and thereby reduce the starting bias in the simulations. Here we present all-atom molecular dynamics simulations of the OmpE36 porin in an outer membrane model which sum up to a simulation time of more than 20 μs and identify the geometrical properties of the first LPS shell and the role of calcium ions in LPS binding to the protein. The simulations reproduce LPS binding to the porin observed in a recently determined crystal structure but not as compact as in the crystal structure. In addition, the influence of the outer membrane environment on the protein dynamics was analyzed. Our findings highlight the role of divalent cations in stabilizing the binding between proteins and LPS molecules in the outer membrane of Gram-negative bacteria.
