AN EFFICIENT DIRECT METHOD FOR GEOMETRY OPTIMIZATION OF LARGE MOLECULES IN INTERNAL COORDINATES

A new efficient procedure has been developed for geometry optimization of large molecules using internal coordinates. The method stores only the nonzero elements of the large transformation matrices, in the spi rit of direct methods in electronic structure theory. Matrix inversion has been replaced by iterative solution of linear systems of equation s by the preconditioned conjugate gradient method. A new incomplete Ch olesky preconditioner proved essential to accelerate the conjugate gra dient procedure, The geometries of several alpha helical alanine polyp eptides, up to 50 alanine units, have been optimized by the new method , using the SYBYL force field. For larger systems, the number of energ y/gradient evaluations is reduced by a factor of 6-10, compared to Car tesian optimization, and the cost of the optimization is small compare d to the energy calculation, We expect this method to be useful in mol ecular mechanics and in mixed quantum mechanics/molecular mechanics ca lculations. (C) 1998 American Institute of Physics. [S0021-9606(98)301 40-3].