Protein Folding

  The problem of how a 1-D poly peptide chain acquires the form of a native 3-D protein structure is referred to as the protein folding problem.
This is one of the most challenging and important research areas in Biochemistry. All the information needed to specify the protein's 3-D structure is contained within its amino acid sequence, and given suitable conditions, most proteins will spontaneously fold into their native states.
Although studies have provided much information on the folding process, our understanding of a way proteins fold is not full yet.

  1. The main reasons the protein folding problem is considered such a difficult one are:if a protein had to search all the possible conformations to find the energetically most favorable one, even a small protein would have to search for an unreasonable amount of time. Since it is known that proteins usually fold into their native states within much shorter time, it is clear that the protein retains partially correct intermediate rather than randomally scan all its possible conformations. Therefore, the energy calculations involve millions of atomic interactions, and going over all of them to find the most favorable conformation is beyond the ability of even the most powerful computers available today.
  2. Structure is much more conserved than sequence. Similar sequences usually give similar structures, but different sequences may lead to a similar structures. As a result, there is a much smaller number of known structures than sequences. This means that the relationship between sequence and structure is not one-to-one, and the tules that predict the structure out of the sequence are not fully understood.
There are several methods to devise the 3-D structure of a protein: