RECURRENCE QUANTIFICATION ANALYSIS IN STRUCTURE-FUNCTION-RELATIONSHIPS OF PROTEINS - AN OVERVIEW OF A GENERAL METHODOLOGY APPLIED TO THE CASE OF TEM-1 BETA-LACTAMASE

Protein structure-function relationships have been increasingly scruti nized by a variety of correlational and information theoretic measures . In an effort to extend this methodology, a technique originally deve loped in nonlinear science, recurrence quantification analysis, was co mbined with traditional principal components analysis to study a large number (56) of TEM-1 beta-lactamase mutants. The hydrophobicity profi les corresponding to the primary structure of 13 naturally occurring m utations partially impairing function, together with 43 artificial non -tolerated mutations were subjected to discriminant analysis, derived from the results of recurrence quantification analysis, coupled to a p rincipal exponents extraction. Eleven (85%) of the naturally occurring mutants and 36 (84%) of the artificial mutants were correctly classif ied (p < 0.0001). We conclude that this technique may be useful in pro tein engineering and, in general, in structure-function studies of bio polymers.