THE ROLE OF THE PHYSICAL SCIENCES IN BIOMEDICAL RESEARCH DAN W. URRY, Ph.D.* and HENRY EYRING, P/i.D.f I. Introduction Physical sciences contribute to biomedical research by introducing new investigative tools, instrumental methods, and physical and chemical techniques. Physical sciences also purvey principles and basic concepts such as thermodynamics, equilibrium theory, and reaction-rate theory. The role of the physical sciences in biomedical research also is to provide appropriate theoretical interpretations which will allow more than empirical utilization of the experimental data obtained using the physical methods. Few single events have had a greater mutual impact on themedical and physical sciences than Roentgen's discovery of X-rays. In the medical sciences radiology has achieved a prominent position in clinical diagnosis; in the physical sciences X-rays have disclosed information on the structure of the atom, and X-ray diffraction affords almost direct observation of molecular structure. In general, physical methods functioning as extensions ofhuman sense perception are performing expanding roles in basic and applied research and in diagnosis and treatment ofdisease. This article treats the physical methods of absorption spectroscopy, fluorescence, and optical rotatory dispersion as applied to the determination of protein conformation. With these instruments, information on protein structure can be obtained and changes in protein conformation can be detected in media approximating that of the physiological state, and most important the means ofobservation does not affect the property under study. Emphasis will be placed on the interpretation ofexperimental * Department of Chemistry, Harvard University, Cambridge, Massachusetts. Appreciation is expressed to the National Science Foundation grant 1328 for its partial financial support. t Department ofChemistry, University ofUtah, Salt Lake City, Utah. 45? Dan W. Urry and Henry Eyring · Physical Sciences in Biomedical Research Perspectives in Biology and Medicine · Summer 1966 data employing primarily the concept of a dipole-interaction potential. However, at the outset we will discuss certain properties of polymers and the role of protein conformation in biological stereospecificity, in enzyme catalysis, in cellular control mechanisms, and in adaptations to specific physiological roles. II. Protein Conformation and Physiological Processes For all its complexity the living organism is constructed from a relatively few basic units, all ofwhich are well characterized in physical and chemical terms. The sugars of which polysaccharides are composed, the amino acids ofwhich proteins are constituted, the nucleotides from which nucleic acids are formed, and the isoprenoid unit (itselfderived fromacetic acid) from which sterols, steroids, and some vitamins are fashioned—these monomeric units have well-defined physical and chemical properties. There is also every reason to believe that the polymer may be described in similar terms, for the determination of the amino-acid sequence of insulin by Sanger [i] verified that proteins have a regular primary structure . The X-ray work on myoglobin [2, 3] and hemoglobin [4, 5] shows these important biomolecules to be regular in all their interactions including those ofthe prosthetic groups. The X-ray crystallography ofthe core of the genetic material [6] discloses deoxyribonucleic acid to be a regular, double-stranded, helical, hydrogen-bonded structure, and, as such, its function in transmitting characteristics from parent to offspring, that is, in specifying a unique set of proteins, is understandable in the light of the principles of chemistry and physics. As much has been said relative to the energetics of living systems, with emphasis on the high degree of organization and the resultant problem ofnegative entropy, it may be mentioned that a simple calculation ofthe sun's energy required for the biological synthesis ofa protein such as myoglobin clearly indicates that there is an inefficient excess offree energy to expend for this negative entropy. Thus it would appear that thermodynamics is held inviolate in the whole living organism as is demonstrable with its component parts. PROPERTIES OF POLYMERIC SYSTEMS It is evident that a regular array, whether it be a molecular crystal, helical protein, or helical nucleic acid, has properties distinct from the randomly oriented monomers. Thus, as is explained by Davydov's theory 4SI of molecular excitons [7], a single absorption maximum in a molecule splits into two or more maxima when in a molecular crystal. This is no less true in helical biopolymers. For, as predicted by Moffitt [8...
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Jan 1, 1993
Xiaofeng Pang 
Open Access