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Restrained simulated annealing was performed using the Merck molecular force field as implemented in Sybyl. Initial structures were taken from DYANA simulations. NOE derived restraints were included using a flat well potential (range constraints in Sybyl). Constraints of 0-3, 0-4, 0-5 Å plus corrections for pseudo atoms were employed for strong, medium, and weak NOEs, respectively. The molecules were equilibrated for 2 ps at 1000 K and cooled linearly to 200 K over 10 ps with 0.5 fs time steps. The resulting structure was used as the input for the following annealing cycle. Typically, 10-20 cycles were run. A constant dielectric of 9.0 was employed to simulate dichloromethane. Final structures were minimized without constraints and represented local minima.
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