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

J Comput Aided Mol Des. 2015 Jan;29(1):13-21. doi: 10.1007/s10822-014-9792-5. Epub 2014 Nov 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / chemistry
  • Acetylglucosamine / metabolism*
  • Antimicrobial Cationic Peptides / chemistry*
  • Antimicrobial Cationic Peptides / metabolism*
  • Binding Sites
  • Disaccharides / chemistry
  • Disaccharides / metabolism
  • Molecular Dynamics Simulation*
  • Plant Lectins / chemistry*
  • Plant Lectins / metabolism*
  • Protein Binding
  • Protein Conformation
  • Thermodynamics


  • Antimicrobial Cationic Peptides
  • Disaccharides
  • Plant Lectins
  • hevein
  • N,N-diacetylchitobiose
  • Acetylglucosamine