PREDICTING IMMUNOGLOBULIN-LIKE HYPERVARIABLE LOOPS

A two-stage method is developed to search the conformational space of small protein segments for low energy structures. Central features of the method are efficient procedures for generating small, eight-backbo ne atom, focal moves in Cartesian coordinates and for introducing geom etric constraints in adaptable Monte Carlo procedures. This allows nat ural implementation of an adaptive simulated annealing algorithm, whic h achieves an effective trade-off between speed and acceptance ratio. The method is applied to the calculation of various immunoglobulin loo ps. We also develop data base derived rules for identifying constraint conditions, and show that the incorporation of an identified side-cha in constraint allows a 1.2 Angstrom all-backbone atom rms deviation pr ediction of a 9 residue long L1 loop. (C) 1994 John Wiley & Sons, Inc.