ULTIMATE COMPUTING - Quantum Consciousness Studies

Protein Conformational Dynamics 133
an iron containing protein in red blood cells which carries oxygen from the lungs
to the various body tissues like brain, heart, or muscle. Hemoglobin which binds
an oxygen molecule is in a different conformation (“oxyhemoglobin”) than
hemoglobin without oxygen (“deoxyhemoglobin”). The conformational state of
hemoglobin found inside red blood cells determines the protein’s capacity to bind
or release oxygen. Hemoglobin conformation is determined by factors which
include the availability of oxygen, temperature, pH, presence of certain other
molecules (i.e. 2,3 DPG), and the amount of nearby oxyhemoglobin. The latter
describes a “collective” effect; when a critical amount of hemoglobin binds
oxygen, the oxyhemoglobin conformation is easier to attain for the remaining
protein molecules. This results in a “sigmoid” shape to the curve which describes
oxygen/hemoglobin binding. The nature of this collective phenomenon is an
indication of the behavior of protein assemblies.
Different frequencies of conformational changes coexist cooperatively in the
same protein (Table 6.1). Some totally reversible conformations like
oxyhemoglobin persist for tens of seconds; others can be very short-lived (i.e.
femtoseconds: 10 -15 seconds), or very long (minutes to hours). The
oxyhemoglobin conformation persists until the oxygen molecule is delivered to
the tissue whose mitochondria use it to produce ATP and GTP. To reach their
binding sites within hemoglobin’s central core, oxygen molecules diffuse through
transient packing defects in the protein’s structure. Nanosecond scale,
conformational “breathing” permits the oxygen molecules to slip in and out,
dependent on surrounding pH, temperature, hormones and other factors. There
thus appear to be at least two levels of conformational states in hemoglobin. The
“functional” conformation (binding vs no binding of oxygen) are relatively long
lasting (long enough to carry oxygen from the lungs to tissue for delivery). In
addition there are more rapid conformational vibrations such as the nanosecond
“breathing” which facilitates diffusion of oxygen molecules through hemoglobin
to reach their binding sites.
Amplitude of motions
Energy
Time Range
Time for collective,
functional steps
Types of motion
0.001 nanometer to 10 nanometers
0.1 kilocalories to 100 kilocalories
10 -15 sec (femtosecond)
to 10 3 sec (many minutes)
10 -9 sec (nanoseconds)
local atom fluctuations
side chain oscillations
displacements of loops, arms, helices,
domains and subunits
collective elastic body modes,
coupled atom fluctuations,
solitons and other nonlinear motions,
coherent excitations
Table 6-1: Protein Conformational Dynamics—Motions of Globular Proteins at
Physiological Temperature (Modified from Karplus and McCammon, 1984).
The vast majority of processes of biological interest are in the time scale
greater than one nanosecond, which also lies in the collective mode realm for
protein dynamics (Karplus and McCammon, 1984). Protein conformational
changes in the nanosecond time frame are able to be coupled to a stimulus and
result in a functional conformational change. Three fundamental features appear
to control these functional states: hydrophobic interactions, charge redistribution