Evolution acting on the same target, but at multiple levels: Proteins as the test case

B Jagadeeshwar Rao
2017 Journal of Biosciences  
Editorial Evolution acting on the same target, but at multiple levels: Proteins as the test case My first Editorial, I thought, would be an excellent platform to share some interesting, less appreciated facets of biology, taking cues from our own research findings, melding them with others in the field and take the issue forward. The editorial is written in way so that less of my own complexity appears and only the complexity that is innate to biology is showcased. Biology, at any length and
more » ... t any length and time-scales of study, is not only exciting but also very intriguing. I will, in my successive editorials, move into various scales of biology, only to wonder about its inner workings. We all know that protein active sites are shaped into executing specific chemical transformations via the steps of catalysis. Therefore, an active site is really the 'business end' of a protein when it is an enzyme, where the directional nature of spatial and charge transfers within the active site seems to mediate the act of catalysis. Active site predictions in a protein must, therefore, invoke methods that combine and compare both spatial congruence and electrostatic potentials of putative active site residues with those in bona fide active site motifs. Methods that successfully perform spatial matches of motifs are fairly abundant (Kleywegt 1999; Goyal et al. 2007; Debret et al. 2009 ), while those that factor in electrostatic potential comparisons are somewhat rare, even today. We realized this deficit sometime back and tried to develop a method that showed that electrostatic potential difference (PD) between analogous residue pairs in an active site from different proteins of the same enzyme family are similar and therefore can be effectively combined with spatial matching methods. That means we found strong correlation in the electrostatic PD between sets of cognate residues in active sites, where for a given enzymatic activity, pairs of residues in an active site from various proteins of the same family yield highly correlated electrostatic PD with very small standard deviation where all such PD's lie in a narrow band. Using this robust finding, we pruned out false matches from spatial congruence sets and offered an additional filter for improving accuracy in active site prediction. By demonstrating conservation of electrostatic potential differences in cognate pairs of residues in a wide range of related proteins, we established a computational method, CataLytic
doi:10.1007/s12038-017-9672-y pmid:28229958 fatcat:6ekl4rqdqfaqdd3jivprdicsjq