NMR Investigations on Ruggedness of Native State Energy Landscape in Folded Proteins

Abstract

The ability of proteins to adopt their functional, highly structured states in the intracellular environment during and after its synthesis is one of the most remarkable evolutionary achievements of biology. Deciphering the code of protein self-organization process has been an intellectual challenge for scientists over the past few decades. Although the structurefunction paradigm about folded structures and functions remains valid, the role of internal dynamics and conformational fluctuations in protein function is becoming increasingly evident (Bhabha et al 2011; Boehr et al 2006; Eisenmesser et al 2005; Fraser et al 2009; Mittermaier and Kay 2006; Parak 2003b; Popovych et al 2006; Tzeng and Kalodimos 2009; Whitten et al 2005). Further, recent structural and genomic data have clearly shown that not all proteins have unique folded structures under normal physiological conditions. Hence, the way a protein exists, is bound to have a profound effect on its function.