Ramachandran redux

摘要

Protein molecules are indispensable to life processes, ranging from catalysis of reactions to transport, signaling, and shaping of cells (1). Despite their intricate architecture, revealed in thousands of 3D structures stored in the Protein Data Bank (2), protein structures rest on a surprisingly small set of principles (1). Perhaps most fundamental of all is the fact that the amide bond (Fig. 1A) is planar, so that only two dihedral angles, denoted by Φ and Ψ (Fig. 1A), define the conformation of the bond linking adjacent amino acids. Following leads from their studies of the structure of collagen, the predominant protein in humans, the crystallographer G. N. Ramachandran and his colleagues first used a 2D diagram to depict the geometry of a dipeptide-two amino acids together with the intervening amide bond (3). They plotted values of one of the angles along the x axis and the second along the y axis, as shown in Fig. 1B. Using the few peptide structures then available, they could see that the angles clustered in only a few sections of the map. Model building led them to conclude that most values of the two angles were inaccessible owing to collisions between atoms of the backbone (Fig. 1B). It is hard to overstate the seminal impact of this representation, which has guided the thinking of protein chemists and structural biologists for many decades, as pointed out by Porter and Rose (4). The article in PNAS by Porter and Rose (4) reports on a unique and quite surprising aspect of the structure of proteins. They have refined the classic Ramachandran plot to introduce the effect of hydrogen bonds (H-bonds) explicitly and are thus able to identify a disfavored bridge region linking the extended β/polyproline Ⅱ (PPⅡ) domain with the αR-basin.