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

Thomas B Woolf, Michael Tychko

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)694-707
Number of pages14
JournalBiophysical Journal
Volume74
Issue number2 I
StatePublished - Feb 1998

Fingerprint

Fatty Acid-Binding Proteins
Ligands
Muscle Proteins
Molecular Dynamics Simulation
Oleic Acid
Molecular Computers
Monounsaturated Fatty Acids
Proteins
Unsaturated Fatty Acids
Adipocytes
Fatty Acids
Amino Acids

ASJC Scopus subject areas

  • Biophysics

Cite this

Simulations of fatty acid-binding proteins. II. Sites for discrimination of monounsaturated ligands. / Woolf, Thomas B; Tychko, Michael.

In: Biophysical Journal, Vol. 74, No. 2 I, 02.1998, p. 694-707.

Research output: Contribution to journalArticle

@article{5f5e1c900a134bca9691304b4d70baab,
title = "Simulations of fatty acid-binding proteins. II. Sites for discrimination of monounsaturated ligands",
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.",
author = "Woolf, {Thomas B} and Michael Tychko",
year = "1998",
month = "2",
language = "English (US)",
volume = "74",
pages = "694--707",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "2 I",

}

TY - JOUR

T1 - Simulations of fatty acid-binding proteins. II. Sites for discrimination of monounsaturated ligands

AU - Woolf, Thomas B

AU - Tychko, Michael

PY - 1998/2

Y1 - 1998/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0031904722&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031904722&partnerID=8YFLogxK

M3 - Article

C2 - 9533683

AN - SCOPUS:0031904722

VL - 74

SP - 694

EP - 707

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 2 I

ER -