Re: How do elements on amino acid chains affect proteins?

To whom it may concern,

Unfortunately, this deceptively simple question does not have short answer. 
 In fact, whole textbooks are devoted to the subject, but I'll try to keep 
it brief.

There are a few fundamental types of interactions that are important in 
describing all biological macromolecules.

(1)  Covalent interactions

(2)  Non-covalent interactions

(3)  Charge-charge interactions

(4)  Hydrogen-bonding interactions

Covalent interactions are simple bonds formed by shared electrons.  A good 
example is methane (CH4), which has four hydrogen atoms covalently bonded 
to a single carbon atom.  Non-covalent interactions are what occur between 
two individual methane molecules.  They are low in energy compared to 
covalent bonds; in fact, these are not described as "bonds" at all, rather 
they describe the "stickiness" of two atoms that contact one another.  
(They have important consequences in the context of other types of 
interactions, which we'll get to in a second).  Charge-charge interactions 
are simple electronic attraction or repulsion forces that occur between 
opposite or like charges, respectively.  The energy associated with ionic 
bonds are typically larger than non-covalent interactions, but can be 
exerted over a long distance.  Unlike covalent bonds that can only exist 
between atoms that contact each other, ionic interactions can be felt over 
a longer distance, even with several (non-interacting) atoms present 
between the charged atoms.  Note too that atoms need not have permanent 
charges to exert or feel the effect of other charged (or polar) atoms; 
partial charges can be just as important.  Actually, some non-covalent 
bonds can be though of as interactions between partially charged atoms.

Hydrogen-bonding interactions occur in the context of nitrogens, oxygens 
and protons, involving a sharing of protons between the heavy atoms and 
lone-pair electrons.  The hydrogen is covalently attached to either an 
oxygen or a nitrogen atom; the hydrogen bond is formed by a sharing of the 
hydrogen with lone-pair electrons on a neighboring oxygen or nitrogen atom. 
 The hydrogen wants to hop back and forth between the oxygens/nitrogens, 
but is held in place by a covalent bond; in reality, the hydrogen (which is 
really just a proton) is partially shared with the hydrogen-bonded atom.  
The best example of these bonds can be found in ice; the crystal structure 
of frozen water is characterized by hydrogen bonds between the protons on 
one water molecule and the lone-pair oxygen electrons of two neighbouring 
water molecules.

In regards to forces that define protein structure, covalent bonds are 
trivial, since they are typically fixed (unless we're talking about an 
enzyme-catalyzed reaction, and we're not).  Proteins are made up of amino 
acids that are linked together as a heteropolymer through covalent 
interactions.  Think of a protein as a candy necklace, where the individual 
candies correspond to different amino acid types.  The other three types of 
interactions are what takes that string of amino acids and stabilizes a 
unique structure that results in a functional protein.  Before we go 
further, we need to talk about what makes a protein a functional protein.

All naturally occurring proteins have a unique topology that is defined by 
the interactions of the individual amino acids side chains (the individual 
candy pieces), as well as the common polymer portion (the string part of 
our candy necklace).  The secondary structure is formed by hydrogen bonds 
involving nitrogen and oxygen atoms on the peptide backbone (polymer, 
string part) of the protein; these secondary structures can look like 
helices or sheets.  The globular structure is formed by these basic 
building blocks that are then held in place by a combination of forces, the 
final result being to collapse the candy-necklace into a densely-packed, 
unique structure.

Hydrophobic and hydrophilic interactions play an important role in defining 
the inside from the outside.  Hydrophilic (water-loving) interactions exist 
between charged amino acids and water; these can be ionic interactions, 
induced-dipole non-covalent interactions, or hydrogen-bonding interactions. 
 Hydrophobic (water-fearing) interactions can be described schematically by 
a mix of oil and water.  (Go to your kitchen and mix vegetable oil with 
water as a demonstration of hydrophobicity).  Water can not hydrogen-bond 
with protons attached to carbon, so it is energetically unfavorable for a 
water molecule to be in contact with aliphatic groups (oily hydrocarbons) 
relative to bulk water (where hydrogen-bonds are easy to form).  Therefore, 
water prefers to interact with other water molecules, not with hydrophobic 
groups.  Finally, non-covalent interactions are favorable between 
hydrophobic groups, though energetically the associative energy is smaller 
in magnitude than the repulsion from water.  The combination of these 
effects gives rise to what we generically refer to as the hydrophobic 
effect.

Since a protein is a mixture of hydrophobic and hydrophilic amino acids, 
they tend to fold up such that hydrophilic groups are in contact with water 
and hydrophobic groups are sequestered in the center of the protein.  This 
alone would not be enough to confer a unique, and functional tertiary 
structure to a particular amino acid sequence.  It's the combination of 
stable secondary structure formation resulting from the nitrogen and oxygen 
atoms on the polymer backbone that form the bricks, while the combination 
of all other types of interactions between amino acid side chains form the 
mortar between the bricks.

For further reading, you should consult a basic Biochemistry (collegiate) 
textbook for details of protein structure.  Any local college library 
should have any number of them to chose from.

Regards,
Dr. James Kranz