Binding energy calculations for hevein–carbohydrate interactions using expanded ensemble molecular dynamics simulations
- 363 Downloads
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.
KeywordsBinding energies Expanded ensemble molecular dynamics Carbohydrates Docking
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.
- 10.Shivakumar DM, Graves AP, Boyce S, Case DA, Shoichet BK (2008) Abstracts of Papers of the American Chemical Society 236Google Scholar
- 11.Shivakumar DM, Case DA (2006) Abstracts of Papers of the American Chemical Society 232: 107Google Scholar
- 21.Hamelberg D, McCammon JA (2004) Abstracts of Papers of the American Chemical Society 227: U1007Google Scholar
- 22.Conformational Analysis Tools <http://www.md-simulations.de/CAT/>. Accessed
- 28.Singh N, Warshel A (2010) Proteins Struct Funct Bioinform 78(7):1705Google Scholar