Biomedical subjects

Hans Frauenfelder

Publications and source records attributed to Hans Frauenfelder.

5 recordsLinked to original sources

PubMed2005

Mosaic energy landscapes of liquids and the control of protein conformational dynamics by glass-forming solvents.

Using recent advances in the Random First-Order Transition (RFOT) Theory of glass-forming liquids, we explain how the molecular motions of a glass-forming solvent distort the protein's boundary and slave some of the protein's conformational motions. Both the length and time scales of the solvent imposed constraints are provided by the RFOT theory. Comparison of the protein relaxation rate to that of the solvent provides an explicit lower bound on the size of the conformational space explored by the protein relaxation. Experimental measurements of slaving of myoglobin motions indicate that a major fraction of functionally important motions have significant entropic barriers.

Chemistry, Physical↗

PubMed2005

Picosecond thermometer in the amide I band of myoglobin.

The amide I and II bands in myoglobin show a heterogeneous temperature dependence, with bands at 6.17 and 6.43 microm which are more intense at low temperatures. The amide I band temperature dependence is on the long wavelength edge of the band, while the short wavelength side has almost no temperature dependence. We compare concepts of anharmonic solid-state crystal physics and chemical physics for the origins of these bands. We suggest that the long wavelength side is composed of those amino acids which hydrogen bond to the hydration shell of the protein, and that temperature dependent bands can be used to determine the time it takes vibrational energy to flow into the hydration shell. We determine that vibrational energy flow to the hydration shell from the amide I takes approximately 20 ps to occur.

Amides↗

PubMed2004

Bulk-solvent and hydration-shell fluctuations, similar to alpha- and beta-fluctuations in glasses, control protein motions and functions.

The concept that proteins exist in numerous different conformations or conformational substates, described by an energy landscape, is now accepted, but the dynamics is incompletely explored. We have previously shown that large-scale protein motions, such as the exit of a ligand from the protein interior, follow the dielectric fluctuations in the bulk solvent. Here, we demonstrate, by using mean-square displacements (msd) from Mossbauer and neutron-scattering experiments, that fluctuations in the hydration shell control fast fluctuations in the protein. We call the first type solvent-slaved or alpha-fluctuations and the second type hydration-shell-coupled or beta-fluctuations. Solvent-slaved motions are similar to the alpha-fluctuations in glasses. Their temperature dependence can be approximated by a Vogel-Tammann-Fulcher relation and they are absent in a solid environment. Hydration-shell-coupled fluctuations are similar to the beta-relaxation in glasses. They can be approximated by a Ferry or an Arrhenius relation, are much reduced or absent in dehydrated proteins, and occur in hydrated proteins even if embedded in a solid. They can be responsible for internal processes such as the migration of ligands within myoglobin. The existence of two functionally important fluctuations in proteins, one slaved to bulk motions and the other coupled to hydration-shell fluctuations, implies that the environment can control protein functions through different avenues and that no real protein transition occurs at approximately 200 K. The large number of conformational substates is essential; proteins cannot function without this reservoir of entropy, which resides mainly in the hydration shell.

Animals↗

PubMed2002

Hydration, slaving and protein function.

Protein dynamics is crucial for protein function. Proteins in living systems are not isolated, but operate in networks and in a carefully regulated environment. Understanding the external control of protein dynamics is consequently important. Hydration and solvent viscosity are among the salient properties of the environment. Dehydrated proteins and proteins in a rigid environment do not function properly. It is consequently important to understand the effect of hydration and solvent viscosity in detail. We discuss experiments that separate the two effects. These experiments have predominantly been performed with wild-type horse and sperm whale myoglobin, using the binding of carbon monoxide over a broad range of temperatures as a tool. The experiments demonstrate that data taken only in the physiological temperature range are not sufficient to understand the effect of hydration and solvent on protein relaxation and function. While the actual data come from myoglobin, it is expected that the results apply to most or all globular proteins.

Animals↗

PubMed2002

Proteins: paradigms of complexity.

Proteins are the working machines of living systems. Directed by the DNA, of the order of a few hundred building blocks, selected from 20 different amino acids, are covalently linked into a linear polypeptide chain. In the proper environment, the chain folds into the working protein, often a globule of linear dimensions of a few nanometers. The biologist considers proteins units from which living systems are built. Many physical scientists look at them as systems in which the laws of complexity can be studied better than anywhere else. Some of the results of such studies will be sketched.

Animals↗