why the protein folding problem isn't really a problem anymore
You may have read the occasional article in the New York Times
science section, or BBC online, about the 'Protein Folding problem'
and how it's one of the last great frontiers of theoretical physics.
That might have been true 15 years ago but, although no
biophysicist will admit it in public, the problem
has been solved for some time now. I'll explain:
Proteins bend and twist into a unique three-dimensional shape
which determines their properties and utility in metabolism and
cellular structure. Which particular three dimensional shape
a particular protein takes is usually determined solely by it's
amino acid sequence. What that means is that the forces which
cause a protein to adapt it's conformation are the result of a
combination of different kinds of intramolecular forces, i.e.
hydrogen bonding, electrostatic interactions,
van der waals interactions, and the hydrophobic effect.
These forces are at this this time well enough understood to
be modeled accurately on a computer. By this I mean that small
organic molecules like phenol can have their structures transcribed into
a program like GAUSSIAN 99 (a quantum mechanical
program which calculates wavefunctions of molecules or
sets of molecules) and the program will predict not only their
conformation but the strength and conformation of their interactions
with other molecules.
These kinds of calculations are extremely computationally
intensive, and the computational cost increases exponentially with
the number of atoms in the system of molecules which one models.
Obviously then a full protein, which contains upwards of 1000
atoms in a favorable case, is not accessible to today's computers.
This is why for the last 30 years or so many biophysicists
have been trying with little success to find broadly applicable
simplifications of these quantum mechanical models so that proteins
can be modeled successfully. However, despite some unfortunate
claims, this has still not worked.
During this time period computational power has increased
exponentially (see Moore's law.) Small peptides can now
be modelled accurately just as simple things like phenol were
10 years ago without any simplifications or approximations.
It doesn't take a genius to decide that within a few years,
entire protein structures will be modeled quantum mechanically.
IBM has figured this out, and it wants to get there first.
Which is why it's building blue gene. When they start
determining the structures of all these new genes that we don't know
anything about that have appeared lately due to the human genome
project, they will patent them immediately, and make bucketloads
of pharmaceutical money on the new drugs designed on the basis
of these structures.