The daunting challenge in the era of Proteomics is to identify the functions of all the proteins identified by the Genomic Project and to elucidate the interplay among these proteins in governing the normal activities of organisms. One approach is to define the structural folds of these proteins. However, a meaningful structure-function correlation depends on an understanding of the unique properties associated with these structural folds. We are studying various folds, namely, the TIM barrel which is the basic fold of hundreds of enzymes; PDZ fold involved extensively in signal transduction; globulin fold in viral envelop proteins and the helix-turn-helix motif adopted by many DNA binding proteins. The approaches are biophysical solution chemistry in conjunction with structural biology, computation chemistry and molecular biology.