Question

64. Computationally predicting protein structure from a sequence may involve a “homology modeling” approach and/or “ab initio” techniques such as fragment assembly. Describe how both evolutionary data and knowledge of physico-chemical principles / force fields are used in predicting the structure adopted by a protein sequence.

Answer 1

A protein sequencing a generally performed by combination of both, in silico information and simulation as well as comparative physico-chemical behavior with respect to other proteins. In this regard, the example of enzyme rennet can be taken for understanding. We known that rennet is a peptidase found in the stomach of the calves. Humans also contain gastric peptidase but they get deactivated or down-regulated generally after 10-15 years of age. However, the rennet in the calves remains active for their life time.

In order to understand the structural features of rennet and human peptidase called pepsin, their structural composition and geometry is first matched along with their numerous biochemical properties such as size, moelcular weight, optimum pH for their activation, stability etc. This forms the physico-chemical analysis of the two proteins, where the structure of rennet is required to be known.

Further, the genetic squences of both proteins are fed into an in silico system and allowed to BLAST. The extent of relatedness of these sequences thus represent the evolutionary symmetry or history of these two enzymes. This represents the evolutionary as well as in silico part of the analysis.

Finally, the simulated structural formation and in silico conformation of the two proteins can be matched simultaneously and the specific features of rennet can be demonstrated as compared to pepsin.

This explains the cohesive role of in silico as well as physico-chemical analysis for structural, evolutionary and conformation relatedness between two proteins, or a novel protein.