Biomedical subjects

Rufus Lumry

Publications and source records attributed to Rufus Lumry.

4 recordsLinked to original sources

PubMed2003

Uses of enthalpy-entropy compensation in protein research.

Cooperative systems of proteins and small molecules form most of biology but are so weakly linked that conventional mass-law formalism requiring exact stoichiometry is inapplicable. The weaknesses cannot be eliminated but using selected families of reactions useful fragmentation of those quantities is often possible. Extra-thermodynamic treatments based on linear-free-energy relationships (LFE) are developed to utilize enthalpy, entropy and volume information not otherwise reliable Linkage systems build around mesophilic proteins are well suited to enforced marriage of linear equations and scaled molecule detail because the ratio of substructure sizes on which folded stability depends is independent of total number of amino-acid residues. Conformational changes in physiological function usually no greater than 0.5 A closely scale to linear thermodynamic changes. The formalisms for use of LFE and compensation relationships are modified to eliminate complications that have previously arisen from incorrect inclusion of the thermal parts of enthalpy and entropy changes in free energy changes. The results are used to remove current confusion about the basis of folded stability in proteins and to minimize the quantitative errors arising from classical treatments of denaturation data. The enthalpy to entropy ratio given by the slope of a compensation plot (its 'compensation temperature') is used to characterize protein construction and function so as to extract machine descriptions of protein linkage systems. In this way the 'fragile' nature of the free-energy surfaces of the myoglobin proteins and the 'strong' character of those surfaces of most other mesophiles can be deduced very simply from the Debye-Waller factors obtained in diffraction studies. The major evolutionary achievement in making proteins big is their crystallike phase behavior. That makes entropy exactly as important as enthalpy so the scalar quantities of small-molecule chemistry can be replaced by the vector quantities that appear necessary to make biology possible.

Entropy↗

PubMed2003

Practical limitations on the use of thermodynamic data from isothermal processes.

Enthalpy, entropy and volume data obtained for processes studied in aqueous solvents generally have been assumed to apply to the solute process without consideration of the coupling between the process and the two-state equilibrium of water. Walrafen's confirmation of the latter in 1983 shows that long-debated model to be correct so the enthalpy and entropy contributions to a free-energy change to give unambiguous information must be corrected for the water contribution. The situation is further complicated by differential chemical interaction of amphiphilic solutes with the two water species since experimental complications make correction difficult or impossible. A more general source of error in isothermal experiments is the linkage to the thermal-equilibrium device. That thermal problem discovered only in 1967 is not yet treated in textbooks although it is always a complication in isothermal processes and responsible for a hierarchy of thermodynamic quantities with different levels of reliability. Major consequences for several familiar thermodynamic and extra-thermodynamic methods are examined in terms of relative reliability. In most cases the thermal corrections are restricted by changes in phase state on cooling.

Entropy↗

PubMed2002

Protein substructures and folded stability.

Protein substructures detected in proton-exchange experiments can be described in quantitative detail with the Debye-Waller temperature factors from diffraction studies. The smallest substructures, in mesophilic proteins approximately 12% of the total residues, determine thermodynamic as well as kinetic stability by electrostatic synergism of a few tightly packed clusters about central peptide-peptide hydrogen bonds. Fixed positions of the clusters establish genetic stability of a protein family. The normal product of thermal denaturation above 280 K in dilute buffers, a compact but motile bubble, is formed with positive free-energy change in step from native state the single transition state and smaller negative change in the step from transition state to product. The largest substructures, approximately 80% of the residues, undergo changes in atom free volumes in function that are small relative to coordinate errors in protein diffraction studies but nevertheless describe the most important conformation changes. The criterion of precision in protein construction is approximately 0.05 A and may be found to be smaller when precision in X-ray diffraction improves. The ratio of residues in the two substructures is fixed in mesophiles.

Amino Acid Sequence↗

PubMed2002

Parsimony in protein evolution.

Pohl found the activation enthalpy and entropy for melting of his mesophilic proteins to be linear in the total number of residues and Privalov and colleagues found this same linearity for the standard heat-capacity, enthalpy and entropy changes in the overall melting equilibria. Despite the small samples these results suggest that mesophiles individually, and as a class, are related through a single standard representative. If so, very extensive convergent evolution has provided both great simplification and very sophisticated goals for genome decoding and quantitative description of protein substructures [R. Lumry, The protein primer, http://www.umn.edu.chem. /groupslumry].

Evolution, Molecular↗