HUNTER: A conformational search program for acyclic to polycyclic molecules with special emphasis on stereochemistry

A new conformational search program, HUNTER, connected with the force fields MMP2 and MM3(92) is presented. The program accepts all types of molecules with most different substructures, considers stereochemical facts, and covers conformational space efficiently and completely. The most important facilities are an automated analysis of the stereochemistry including topographical facts, a separate perturbation of the acyclic and cyclic parts of the molecule using modified corner flapping, and an incremental rotation around single bonds with fixed flap and rotation angles, respectively; an exclusion of high energy structures by simulated annealing; the choice of the conformer lowest in energy, which is new as an initial structure for the next sampling run; and the use of a reduced set of dihedral angles to define a conformation. A specifically devised graphic interface, SERVANT, is used to feed in and control all informations necessary for a program run and to visualize the results. Most of the parameters are user-defined and thereby allow a flexible search, including a search for the most stable diastereomer. The efficiency of the different parameter sets was tested in calculation with cycloundecane (12), (Z)-oct-3-ene (13), and sipholenol-A monoacetate (14). The best performance regarding the number of different low-energy conformers was achieved with 60° (14) and 90° flaps (12), respectively, including substituent correction for the cyclic parts, and with 105° (14) and 120° rotations (13), respectively, for the acyclic parts. In comparison to the stochastic search routine implemented in MM3(92), HUNTER performed two (12) to six (14) times better. © 1997 John Wiley & Sons, Inc. J Comput Chem 18: 1264–1281, 1997