TY - JOUR
T1 - Assessing the stabilization of P-glycoprotein's nucleotide-binding domains by the linker, using molecular dynamics
AU - Ferreira, Ricardo J.
AU - Ferreira, Maria José U.
AU - Dos Santos, Daniel J.V.A.
PY - 2013/6
Y1 - 2013/6
N2 - This paper focuses on the importance of the intermediate linker sequence for the stabilization of the cytoplasmic portion of murine P-glycoprotein, an ABC transporter involved in Multidrug Resistance (MDR) in cancer. Three putative protein-protein interaction areas were predicted to exist, two of them next to the C-terminal nucleotide-binding domain (NBD2) and the third one next to the inner leaflet interface of the lipid bilayer. These contact spots were confirmed by detailed contact maps from structures obtained before and after a 100 ns molecular dynamics production run, allowing a more thorough characterization of the type and number of residues involved in protein-protein contacts. It was found that these contact surfaces are located next to several highly conserved motifs of ABC transporters, serving as anchor points and assisting the linker's 'damper' function.
AB - This paper focuses on the importance of the intermediate linker sequence for the stabilization of the cytoplasmic portion of murine P-glycoprotein, an ABC transporter involved in Multidrug Resistance (MDR) in cancer. Three putative protein-protein interaction areas were predicted to exist, two of them next to the C-terminal nucleotide-binding domain (NBD2) and the third one next to the inner leaflet interface of the lipid bilayer. These contact spots were confirmed by detailed contact maps from structures obtained before and after a 100 ns molecular dynamics production run, allowing a more thorough characterization of the type and number of residues involved in protein-protein contacts. It was found that these contact surfaces are located next to several highly conserved motifs of ABC transporters, serving as anchor points and assisting the linker's 'damper' function.
KW - Molecular dynamics
KW - Nucleotide-binding sites
KW - P-Glycoprotein
KW - Protein-protein contacts
UR - http://www.scopus.com/inward/record.url?scp=84879792902&partnerID=8YFLogxK
U2 - 10.1002/minf.201200175
DO - 10.1002/minf.201200175
M3 - Article
AN - SCOPUS:84879792902
SN - 1868-1743
VL - 32
SP - 529
EP - 540
JO - Molecular Informatics
JF - Molecular Informatics
IS - 5-6
ER -