A GENETIC ALGORITHM-BASED MOLECULAR MODELING TECHNIQUE FOR RNA STEM-LOOP STRUCTURES

A new modeling technique for arriving at the three dimensional (3-D) s tructure of an RNA stern-loop has been developed based on a conformati onal search by a genetic algorithm and the following refinement by ene rgy minimization. The genetic algorithm simultaneously optimizes a pop ulation of conformations in the predefined conformational space and ge nerates 3-D models of RNA. The fitness function to be optimized by the algorithm has been defined to reflect the satisfaction of known confo rmational constraints. In addition to a term for distance constraints, the fitness function contains a term to constrain each local conforma tion near to a prepared template conformation. The technique has been applied to the two loops of tRNA, the anticodon loop and the T-loop, a nd has found good models with small root mean square deviations from t he crystal structure. Slightly different models have also been found f or the anticodon loop. The analysis of a collection of alternative mod els obtained has revealed statistical features of local variations at each base position.