EFFICIENCY OF THE LOCAL TORSIONAL DEFORMATIONS METHOD FOR IDENTIFYINGTHE STABLE STRUCTURES OF CYCLIC MOLECULES

A new method for generating the low-energy structures of a chain molec ule was proposed recently by us. This is a stochastic process where at each step an energy-minimized structure is changed by carrying out se veral local torsional deformations (LTDs) along the chain, which tempo rarily disrupt neighbors of the rotated bonds. The energy is then mini mized and the disrupted bonds return to their usual geometry (in terms of bond lengths and angles) while the chain assumes a new conformatio n. This conformation is accepted (and then deformed) or rejected with the help of a ''selection procedure'' that gives preference to accepti ng the lower energy structures and, thug, directs the search toward th e lowest energy regions, which include the global energy minimum (GEM) structure. The selection procedures tested are the Mont Carlo minimiz ation (MCM) method of Li and Scheraga and the ''usage directed'' (UD) method of Still's group. LTD is a general method whose parameters can be optimized for any chain system. However, because of the local chara cter of the conformational change, it is expected to be especially eff icient for cyclic peptides, loops in proteins, and dense multichain sy stems. In this paper, LTD is applied to cycloheptadecane modeled by th e MM2 force field, its parameters are optimized, and it is found to be more efficient than other methods. The results for this molecule and for an ECEPP model of the linear pentapeptide Leu-enkephalin show that MCM and UD are almost comparable in efficiency, with a slight advanta ge for MCM.