ULTIMATE COMPUTING - Quantum Consciousness Studies

144 Protein Conformational Dynamics
The most significant conformational vibrations are suggested by Harvard’s
Karplus and McCammon (1984) to be in the middle of this range: nanoseconds.
Such fluctuations are appropriate for conformational motion of globular proteins
(4 to 10 nanometer diameter), consistent with enzymatic reaction rates and
“coupled modes” like solitons. As an example, Karplus and McCammon describe
a rotation of a tyrosine ring deep inside a globular protein called bovine
pancreatic trypsin inhibitor. The side chain of the amino acid tyrosine includes a
six carbon “aromatic” hexagonal ring with an electron resonance cloud. The
rotation of the ring has been studied experimentally by nuclear magnetic
resonance and Karplus and McCammon have done a computer simulation based
on that data which shows the protein changing conformational state as the
tyrosine ring rotates 90 degrees. The switch occurs in the nanosecond time scale
and is collectively coupled to movement in the polypeptide backbone chain.
Collective nanosecond conformational states have been elegantly woven in a
theory of coherent protein excitations by Professor Herbert Fröhlich who
presently divides his time between Liverpool University and the Max Planck
Institute in Stuttgart. Recognized as a major contributor to the modern theory of
superconductivity, Fröhlich turned to the study of biology in the late 1960’s and
came to several profound conclusions. One is that changes in protein
conformation in the nanosecond time scale are triggered by a charge redistribution
such as a dipole oscillation within hydrophobic regions of proteins (Fröhlich,
1975). Another Fröhlich (1970) concept is that a set of proteins connected in a
common voltage gradient field such as within a membrane or polymer electret
such as the cytoskeleton would oscillate coherently at nanosecond periodicity if
energy such as biochemical ATP were supplied. Fröhlich’s model of coherency
can explain long range cooperative effects by which proteins and nucleic acids in
biological systems can communicate. A major component of Fröhlich’s theory
suggests that random supply of energy to a system of nonlinearly coupled dipoles
can lead to coherent excitation of a single vibrational mode, provided the energy
exceeds a critical threshold. Frequencies of the order of 10 9 to 10 11 Hz are
suggested by Fröhlich, who maintains that the single mode appears because all
others are in thermal equilibrium. Far reaching biological consequences may be
expected from such coherent excitations and long range cooperativity.
Conformation of proteins and their dipole moments in aqueous, physiological
environment are dominated by interaction of their charge groups with surrounding
water and ions. Some biomolecules may possess excited states with very high
dipole moments. These levels, according to Fröhlich, tend to become stabilized
(become “metastable states”) through internal and external deformations and
through displacement of “counter” ions like calcium. Metastable states, which
correlate with functional conformations, are thus collective effects involving the
molecule and its surroundings. A molecule might be lifted into a metastable state
through the action of electric fields, binding of ligands or neurotransmitters, or
effects of neighbor proteins. Thus rapid, nanosecond oscillations may become
“locked” in specific modes which correspond to useful conformations of a
protein. For example an ion channel, receptor, enzyme, or tubulin subunit may
stay in one conformational state for relatively long periods, on the order of
milliseconds. Fröhlich characterizes these conformations as “metastable” states.
Fröhlich observes that the high electric field of the order of 10 7 volts per
meter maintained in many biological membranes (100 millivolts / 10 nanometers
= 10 7 volts/meter) requires an extraordinary dielectric property of the membrane
components including lipids and proteins. Similar requirements would exist for
cytoskeletal proteins in an electret. Ordinary material would suffer dielectric
breakdown in such fields unless specially prepared. Fröhlich contends the