Simulations of fatty acid-binding proteins. II. Sites for discrimination of monounsaturated ligands

Biophysical Journal
T B Woolf, M Tychko

Abstract

Fatty acid binding proteins (FABPs) can discriminate between saturated and unsaturated fatty acids via molecular mechanisms that are not understood. Molecular dynamics computer calculations are used to suggest the relationship between tertiary structure and binding specificity. Three separate 1-ns simulations, with explicit solvent, are presented: 1) oleic acid (C18:1 cis) bound to adipocyte FABP, 2) oleic acid bound to human muscle FABP, and 3) elaidic acid (C18:1 trans) bound to human muscle FABP. The average structural, dynamic, and energetic properties of the trajectory were analyzed, as were the motional correlations. The molecular dynamics trajectories reveal intriguing differences among all three systems. For example, the two proteins have different strengths of interaction energy with the ligand and different motional coupling, as seen with covariance analysis. This suggests distinctive molecular behavior of monounsaturated fatty acids in the two similar proteins. An importance scale, based on motional correlation and interaction energy between protein and ligand, is proposed, to help identify amino acids involved with the discrimination of ligand saturation state or geometric isomerization.

References

Jan 4, 1991·Biochimica Et Biophysica Acta·J H VeerkampR G Maatman
Oct 8, 1990·Molecular and Cellular Biochemistry·J F Glatz, G J van der Vusse
Nov 24, 1995·The Journal of Biological Chemistry·L TeboulP A Grimaldi
Mar 1, 1995·The Proceedings of the Nutrition Society·J H Veerkamp
Feb 1, 1995·Prostaglandins, Leukotrienes, and Essential Fatty Acids·J F GlatzG J van der Vusse
Dec 1, 1994·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J M LaLondeL J Banaszak
Dec 1, 1993·Proteins·A AmadeiH J Berendsen
Jan 1, 1994·Advances in Protein Chemistry·L BanaszakT A Jones
Mar 1, 1994·Protein Engineering·J AqvistJ E Samuelsson
Dec 22, 1995·Journal of Medicinal Chemistry· Ajay, M A Murcko
May 10, 1996·The Journal of Biological Chemistry·G V RichieriA M Kleinfeld
Dec 6, 1996·The Journal of Biological Chemistry·G V RichieriA M Kleinfeld
Sep 1, 1996·Progress in Lipid Research·J F Glatz, G J van der Vusse
Apr 27, 1992·Physical Review Letters·A E García

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Citations

Oct 17, 2009·Journal of Molecular Modeling·Lihie Ben-Avraham LevinYossi Tsfadia
Nov 26, 1999·Biochimica Et Biophysica Acta·A Reese-WagonerL Banaszak
Nov 26, 1999·Biochimica Et Biophysica Acta·G Zanotti
Jun 24, 2003·Biochimica Et Biophysica Acta·Emma JakobssonGerard J Kleywegt
Jul 27, 2012·Journal of Biomolecular Structure & Dynamics·Adriana EstevesMargot Paulino Zunini
Aug 19, 1999·Protein Science : a Publication of the Protein Society·V A Likić, F G Prendergast
Oct 19, 2001·Biophysical Journal·J TorresI T Arkin
Jan 29, 2002·Journal of Molecular Biology·Dirk Bakowies, Wilfred F van Gunsteren
May 29, 2014·Biopolymers·Martiniano Bello, Enrique García-Hernández
Jan 27, 2005·Gastroentérologie Clinique Et Biologique·Valérie MarcilEmile Levy

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