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A new method was proposed by Mongan et al. for constant pH molecular dynamics simulation and was implemented in AMBER 8 package. Protonation states are modeled with different charge sets, and titrating residues are sampled from a Boltzmann distribution of protonation states. The simulation periodically adopts Monte Carlo sampling based on Generalized Born (GB) derived energies. However, when this approach was applied to a bio-toxin, Botulinum Neurotoxin Type A (BoNT/A) at pH 4.4, 4.7, 5.0, 6.8 and 7.2, the predictions yielded by the method were inconsistent with the experimental values. The systems being simulated were divergent. Furthermore, the system behaviors in a very weak acidic solution (pH 6.8) and in a very weak basic solution (pH 7.2) were significantly different from the neutral case (pH 7.0). Hence, we speculate this method may require further study for modeling large biomolecule. [Copyright &y& Elsevier]

Cites a study from the U.S. reporting on the mapping of the synaptosome-binding regions on the heavy chain of botulinum neurotoxin (BoNT/A). Preparation of synthetic overlapping peptides that had uniform size and overlaps and encompassed the entire H chain of BoNT/A; Inhibition of the binding of (I)125-labeled BonT/A to mouse brain synaptosomes by free unlabeled BoNT/A; Manifestation by individual peptides of inhibitory activities greater than 10% on the H-N domain.