INFERRING THE CONFORMATION OF RNA BASE-PAIRS AND TRIPLES FROM PATTERNS OF SEQUENCE VARIATION

The success of comparative analysis in resolving RNA secondary structu re and numerous tertiary interactions relies on the presence of base c ovariations, Although the majority of base covariations in aligned seq uences is associated to Watson-Crick base pairs, many involve non-cano nical or restricted base pair exchanges (e.g. only G:C/A:U), reflectin g more specific structural constraints, We have developed a computer p rogram that determines potential base pairing conformations for a give n set of paired nucleotides in a sequence alignment, This program (ISO PAIR) assumes that the base pair conformation is maintained through se quence variation without significantly affecting the path of the sugar -phosphate backbone, ISOPAIR identifies such 'isomorphic' structures f or any set of input base pair or base triple sequences, The program wa s applied to base pairs and triples with known structures and sequence exchanges. In several instances, isomorphic structures were correctly identified with ISOPAIR, Thus, ISOPAIR is useful when assessing non-c anonical base pair conformations in comparative analysis. ISOPAIR appl ications are limited to those cases where unusual base pair exchanges indeed reflect a non-canonical conformation.