期刊
JOURNAL OF COMPUTATIONAL CHEMISTRY
卷 32, 期 6, 页码 1043-1053出版社
WILEY
DOI: 10.1002/jcc.21683
关键词
cyanovirin-N; binding free energy prediction; MM/PBSA; MM/GBSA; crystal MD simulations
资金
- University of Arizona
Complexes of two Cyanovirin-N (CVN) mutants, m4-CVN and P51G-m4-CVN, with deoxy di-mannose analogs were employed as models to generate conformational ensembles using explicit water Molecular Dynamics (MD) simulations in solution and in crystal environment. The results were utilized for evaluation of binding free energies with the molecular mechanics Poisson-Boltzmann (or Generalized Born) surface area, MM/PB(GB)SA, methods. The calculations provided the ranking of deoxy di-mannose ligands affinity in agreement with available qualitative experimental evidences. This confirms the importance of the hydrogen-bond network between di-mannose 3'- and 4'-hydroxyl groups and the protein binding site B M as a basis of the CVN activity as an effective HIV fusion inhibitor. Comparison of binding free energies averaged over snapshots from the solution and crystal simulations showed high promises in the use of the crystal matrix for acceleration of the conformational ensemble generation, the most time consuming step in MM/PB(GB)SA approach. Correlation between energy values based on solution versus crystal ensembles is 0.95 for both MM/PBSA and MM/GBSA methods. (C) 2010 Wiley Periodicals, Inc. J Comput Chem 32: 1043-1053, 2011
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