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The N‐terminal of annexin A1 as a secondary membrane binding site: A molecular dynamics study
Author(s) -
Donohue Matthew P.,
Bartolotti Libero J.,
Li Yumin
Publication year - 2014
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24623
Subject(s) - terminal (telecommunication) , annexin a2 , annexin , dynamics (music) , binding site , molecular dynamics , chemistry , biophysics , computational biology , microbiology and biotechnology , biology , biochemistry , computer science , physics , computational chemistry , telecommunications , cell , acoustics
Annexin A1 has been shown to cause membrane aggregation and fusion, yet the mechanism of these activities is not clearly understood. In this work, molecular dynamics simulations were performed on monomeric annexin A1 positioned between two negatively charged monolayers using AMBER's all atom force field to gain insight into the mechanism of fusion. Each phospolipid monolayer was made up of 180 DOPC molecules and 45 DOPG molecules to achieve a 4:1 ratio. The space between the two monolayers was explicitly solvated using TIP3P waters in a rectilinear box. The constructed setup contained up to 0.14 million atoms. Application of periodic boundary conditions to the simulation setup gave the desired effect of two continuous membrane bilayers. Nonbonded interactions were calculated between the N‐terminal residues and the bottom layer of phospholipids, which displayed a strong attraction of K26 and K29 to the lipid head‐groups. The side‐chains of these two residues were observed to orient themselves in close proximity (∼3.5 Å) with the polar head‐groups of the phospholipids. Proteins 2014; 82:2936–2942. © 2014 Wiley Periodicals, Inc.