Paper Citing NAMD - Abstract
Yu, Rilei; Kaas, Quentin; Craik, David J.
Delineation of the Unbinding Pathway of alpha-Conotoxin Iml from the alpha 7 Nicotinic Acetylcholine Receptor
JOURNAL OF PHYSICAL CHEMISTRY B, 116:6097-6105, MAY 31 2012
alpha-Conotoxins potently and specifically inhibit isoforms of nicotinic acetylcholine receptors (nAChRs) and are used as molecular probes and as drugs or drug leads. Interactions occurring during binding and unbinding events are linked to binding kinetics, and knowledge of these interactions could help in the development of alpha-conotoxins as drugs. Here, the unbinding process for the prototypical alpha-conotoxin ImI/alpha 7-nAChR system was investigated theoretically, and three exit routes were identified using random accelerated molecular dynamics simulations. The route involving the smallest conformation perturbation was further divided into three subpathways, which were studied using steered molecular dynamics simulations. Of the three subpathways, two had better experimental support and lower potential of mean force, indicating that they might be sampled more frequently. Additionally, these subpathways were supported by previous experimental studies. Several pairwise interactions, including a cation-pi interaction and charge and hydrogen bond interactions, were identified as potentially playing important roles in the unbinding event.
