Name
Title | ||
|---|---|---|
Binding Structures Of Tri-N-Acetyl-Beta-Glucosamine In Hen Egg White Lysozyme Using Molecular Dynamics With A Polarizable Force Field |
Abstract | ||
|---|---|---|
Lysozyme is a well-studied enzyme that hydrolyzes the beta-(1,4)glycosidic linkage of N-acetyl-beta-glucosamine (NAG)(n) oligomers. The active site of hen egg-white lysozyme (HEWL) is believed to consist of six subsites, A-F that can accommodate six sugar residues. We present studies exploring the use of polarizable force fields in conjunction with all-atom molecular dynamics (MD) simulations to analyze binding structures of complexes of lysozyme and NAG trisaccharide, (NAG)(3). MD trajectories are applied to analyze structures and conformation of the complex as well as protein-ligand interactions, including the hydrogen-bonding network in the binding pocket. Two binding modes (ABC and BCD) of (NAG)(3) are investigated independently based on a fixed-charge model and a polarizable model. We also apply molecular mechanics with generalized born and surface area (MM-GBSA) methods based on MD using both nonpolarizable and polarizable force fields to compute binding free energies. We also study the correlation between root-mean-squared deviation and binding free energies of the wildtype and W62Y mutant; we find that for this prototypical system, approaches using the MD trajectories coupled with implicit solvent models are equivalent for polarizable and fixed-charge models. (C) 2012 Wiley Periodicals, Inc. DOI: 10.1002/jcc.23109 |
Year | DOI | Venue |
|---|---|---|
2013 | 10.1002/jcc.23109 | JOURNAL OF COMPUTATIONAL CHEMISTRY |
Keywords | Field | DocType |
protein-ligand binding, force field, molecular dynamics, polarizable, CHARMM, charge equilibration, lysozyme, carbohydrates | Molecular mechanics,Force field (physics),Crystallography,Lysozyme,Binding site,Computational chemistry,Chemistry,Molecular dynamics,Solvent models,Active site,Hydrogen bond | Journal |
Volume | Issue | ISSN |
34 | 3 | 0192-8651 |
Citations | PageRank | References |
1 | 0.35 | 11 |
Authors | ||
2 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Yang Zhong | 1 | 1 | 0.35 |
| Sandeep Patel | 2 | 107 | 12.96 |