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Journal of Computer-Aided Molecular Design

, Volume 29, Issue 1, pp 13–21 | Cite as

Binding energy calculations for hevein–carbohydrate interactions using expanded ensemble molecular dynamics simulations

  • Chaitanya A. K. Koppisetty
  • Martin Frank
  • Alexander P. Lyubartsev
  • Per-Georg NyholmEmail author
Article

Abstract

Accurate estimation of protein–carbohydrate binding energies using computational methods is a challenging task. Here we report the use of expanded ensemble molecular dynamics (EEMD) simulation with double decoupling for estimation of binding energies of hevein, a plant lectin with its monosaccharide and disaccharide ligands GlcNAc and (GlcNAc)2, respectively. In addition to the binding energies, enthalpy and entropy components of the binding energy are also calculated. The estimated binding energies for the hevein–carbohydrate interactions are within the range of ±0.5 kcal of the previously reported experimental binding data. For comparison, binding energies were also estimated using thermodynamic integration, molecular dynamics end point calculations (MM/GBSA) and the expanded ensemble methodology is seen to be more accurate. To our knowledge, the method of EEMD simulations has not been previously reported for estimating biomolecular binding energies.

Keywords

Binding energies Expanded ensemble molecular dynamics Carbohydrates Docking 

Notes

Acknowledgments

The authors thank Prof. Graham J. L. Kemp at the Department of Computer Science and Engineering, Chalmers University of Technology, Gothenburg, Sweden for valuable suggestions and comments on the manuscript. The computational resources at C3SE (www.c3se.chalmers.se) provided by the Swedish National Infrastructure for Computing (SNIC) are gratefully acknowledged. Financial support from Biognos AB is gratefully acknowledged.

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Chaitanya A. K. Koppisetty
    • 1
    • 2
  • Martin Frank
    • 1
  • Alexander P. Lyubartsev
    • 3
  • Per-Georg Nyholm
    • 1
    • 4
    Email author
  1. 1.Biognos ABGothenburgSweden
  2. 2.Department of Computer Science and EngineeringChalmers University of TechnologyGothenburgSweden
  3. 3.Arrhenius Laboratory, Division of Physical ChemistryStockholm UniversityStockholmSweden
  4. 4.Department of Medical Biochemistry, Institute of BiomedicineUniversity of GothenburgGothenburgSweden

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