Molecular mechanism with regard to the binding selectivity of inhibitors toward FABP5 and FABP7 explored by multiple short molecular dynamics simulations and free energy analyses

2020 ◽  
Vol 22 (4) ◽  
pp. 2262-2275 ◽  
Author(s):  
Jianzhong Chen ◽  
Xinguo Liu ◽  
Shaolong Zhang ◽  
Junxiao Chen ◽  
Haibo Sun ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Fatty Acid ◽  
Molecular Dynamics Simulations ◽  
Molecular Mechanism ◽  
Binding Proteins ◽  
Fatty Acid Binding Proteins ◽  
Binding Selectivity ◽  
Fatty Acid Binding ◽  
Dynamics Simulations

Recently, fatty acid binding proteins 5 and 7 (FABP5 and FABP7) have been regarded as the prospective targets for clinically treating multiple diseases related to FABPs.

Molecular dynamics simulations of palmitate entry into the hydrophobic pocket of the fatty acid binding protein

FEBS Letters ◽  
2007 ◽  
Vol 581 (6) ◽  
pp. 1243-1247 ◽  
Author(s):  
Yossi Tsfadia ◽  
Ran Friedman ◽  
Jonathan Kadmon ◽  
Anna Selzer ◽  
Esther Nachliel ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acid ◽  
Molecular Dynamics Simulations ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Hydrophobic Pocket ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Dynamics Simulations

scholarly journals Brain fatty acid binding protein exhibits non-preferential and mutation-resistant binding towards fatty acids

2021 ◽  
Author(s):  
Iulia Bodnariuc ◽  
Stefan Lenz ◽  
Margaret Renaud-Young ◽  
Tanille Shandro ◽  
Hiroaki Ishida ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Molecular Dynamics Simulations ◽  
Nuclear Localization ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Dynamics Simulations

Members of the fatty acid binding protein (FABP) family function as intracellular transporters of long chain fatty acids and other hydrophobic molecules to different cellular compartments. Brain fatty acid binding protein (FABP7) exhibits ligand-directed differences in cellular transport behavior. For example, when FABP7 binds to docosahexaenoic acid (DHA), the complex relocates to the nucleus and influences transcriptional activity, whereas FABP7 bound with monosaturated fatty acids remain in the cytosol. We used a variety of biophysical techniques to enhance understanding of ligand-directed transport. Specifically, we examine how FABP7 binds to fatty acids, including saturated stearic acid (SA), monounsaturated oleic acid (OA), and polyunsaturated DHA. We find that at 37°C FABP7 has near equivalent binding affinities for the fatty acids, while at lower temperatures, FABP7 exhibits a preference for the unsaturated fatty acids. Therefore, nuclear localization of the FABP7-DHA complex cannot be explained by binding preferences. Using NMR spectroscopy and molecular dynamics simulations, we observe that DHA uniquely affects the portal region of FABP7, which could enhance the complex's nuclear localization. Mutations to purported critical binding residues (R126L and Y128F) have little effect on fatty acid binding, with molecular dynamics simulations revealing that the bound fatty acid can adopt binding poses that can accommodate the mutations.

Molecular dynamics study of the interaction between fatty acid binding proteins with palmitate mini-micelles

2009 ◽  
Vol 326 (1-2) ◽  
pp. 29-33 ◽  
Author(s):  
Lihie Ben-Avraham Levin ◽  
Esther Nachliel ◽  
Menachem Gutman ◽  
Yossi Tsfadia
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acid ◽  
Binding Proteins ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding
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