Wednesday, January 18, 2017

The basic premise of protein folding

A molecule is a set of atoms connected to each other by covalent bonds. A covalent bond involves the sharing of an electron pair across two nuclei.  When two atoms are so bonded, their movements relative to each other become very restricted in all degrees of freedom, translational and rotational, except one - rotation on the axis of the bond. Within the domain of temperatures viable to life on Earth, single-bonded atom pairs freely rotate on the bond (though certain angles will be energetically favored over others and may even be forbidden by steric constraints in particular instances).

Polypeptides emerge from the ribosome in an alpha-helix form, effectively a straight rod. The polypeptide then spontaneously folds into its mature form almost exclusively by rotation on the two single bonds internal to each amino acid. All amino acids involved in protein synthesis have a central carbon (CA) with a single bond to a nitrogen (N) and another single bond to another carbon (C) that is itself double bonded to an oxygen (O). When two amino acids are joined by the ribosome, a bond is formed between the C of one and the N of the next. No rotation is seen on this new bond, however, because of the nature of oxygen and nitrogen. Nitrogen has a weaker hold on its electrons than does carbon whereas oxygen has a stronger hold. The result is that an other electron pair is drawn to some degree across the bond between the amino acids preventing rotation on that peptide bond.

The central carbon (CA) of all amino acid species except glycine also single bonds to a third carbon (CB) that further bonds to other atoms depending on the particular amino acid species involved. This so called side chain ( as opposed to the N-CA-C "backbone") must interact with the alpha-helix to direct the folding process since polypeptides differing only in the particular sequence of amino acid types are seen to fold in various but deterministic ways.