The Origami of Protein Folding

Protein Folding is the ability of protein molecules to fold into their highly structured functional states defined by their amino acid sequence. The strings of amino acids that emerge from the protein synthesizing machinery, bend, loop, twist, coil and collapse on itself to produce the finished design as enzymes and other life-sustaining cellular components. The spontaneous self-assembly of these molecules into a unique three-dimensional structure is one of the most remarkable achievements in biology.

Why Fold Proteins?

The growing genome knowledge and the pressing necessity for the discovery of new drug targets for life-threatening diseases bring the protein folding problem to the centre stage of computational molecular biology.

A 3-D structure could yield invaluable insights into the function of unknown proteins, revealing new druggable targets and improving our understanding of cellular processes.

Improvements in structure prediction will lead to improvements in protein design, which can be directly translated into making new enzymes for industrial applications, novel vaccines, and other bio-nanomachines.

Ab initio Approach

Ab initio structure prediction attempts to model proteins by starting from an extended chain and folding up the sequence on the computer. This method has the advantage that it does not depend on a previously determined structure to serve as a template. It is generally assumed that a protein folds to a native conformation that is at or near the global free-energy minimum. Thus, the problem can be decomposed into two sub-problems: (a) developing an efficient energy function and (b) developing an accurate algorithm for searching the resultant energy landscape.

References

  • B Jayaram, Priyanka Dhingra, Avinash Mishra, Rahul Kaushik, Goutam Mukherjee, Ankita Singh, Shashank Shekhar. (2014). Bhageerath-H: A homology ab initio hybrid server for predicting tertiary structures of monomeric soluble proteins. BMC Bioinformatics. Read article
  • Ankita Singh, Rahul Kaushik, Dheeraj Kumar Chaurasia, Manpreet Singh, B Jayaram. (2020). PvP01-DB: computational structural and functional characterization of soluble proteome of PvP01 strain of Plasmodium vivax. Database. Read article
  • Ankita Singh, Rahul Kaushik, Avinash Mishra, Asheesh Shanker, B Jayaram. (2015). ProTSAV: A Protein Tertiary Structure Analysis and Validation Server. BBA - Proteins and Proteomics. Read article