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Biomedical subjects

N Go

Publications and source records attributed to N Go.

At least 91 records · Page 5Linked to original sources
PubMed1981

Combined use of proton-proton Overhauser enhancements and a distance geometry algorithm for determination of polypeptide conformations. Application to micelle-bound glucagon.

In a new approach for the determination of polypeptide conformation, experimental data on intramolecular distances between pairs of hydrogen atoms obtained from nuclear Overhauser enhancement studies are used as input for a distance geometry algorithm. The algorithm determines the limits of the conformation space occupied by the polypeptide chain. The experimental data are used in such a way that the real conformation should in all cases be within these limits. Two important features of the method are that the results do not depend critically on the accuracy of the distance measurements by nuclear Overhauser enhancement studies and that internal mobility of the polypeptide conformation is explicitly taken into consideration. The use of this new procedure is illustrated with a structural study of the region 19-27 of glucagon bound to perdeuterated dodecylphosphocholine micelles.

Amino Acid Sequence↗
PubMed1979

Melting-profile analysis of thermal stability of thermolysin. A formulation of temperature-scanning kinetics.

The melting-profile method consists of a continuous observation of a structural parameter while the temperature of the sample is raised at a constant rate [Fugita, S. C., & Imahori, K. (1974) IN Peptides, Polypeptides and Proteins (Blout, E. R., Bovey, F. A., Goodman, M., & Lotan, N., Eds.) p 217, Wiley, New York, N.Y.]. An analytical solution to the melting profile was formulated for the two-state irreversible process and called temperature-scanning kinetics. The theory was tested with thermolysin with consistent results, and the thermodynamic parameters of thermal denaturation were calculated: deltaH identical to = 80.3 kcal/mol, deltaS identical to = 153 eu. These values agreed with the corresponding values obtained from the classical constant-temperature relaxation kinetics. The possibilities of temperature-scanning kinetics are discussed.

Calcium↗
PubMed1979

Studies on protein folding, unfolding and fluctuations by computer simulation. III. Effect of short-range interactions.

The theoretical model of proteins on the two-dimensional square lattice, introduced previously, is extended to include the specific short-range interactions. Attractive long-range interactions with various specificities and non-specific repulsive long-range interactions in the form of self-avoidance of the polymer chain are also operative in the model. Dynamics of the model protein is studied by a Monte Carlo method. The short-range interactions are found to accelerate the folding and unfolding transitions. Non-specific part of the attractive long-range interactions have a competing effect of decelerating the transitions. When the short-range interactions are weighted beyond a certain extent over the attractive long-range interactions are weighted beyond a certain extent over the attractive long-range interactions, the all-or-none character of the folding and unfolding transitions is destroyed. How the destruction proceeds is quantitatively expressed in terms of the S-H curves. The limiting case of dominance of the specific short-range interactions over the attractive long-range interactions is studied in detail. The lattice polymer in this limit does not behave like a globular protein at all. This observation leads to a reexamination of the currently popular notion of the dominance of the short-range interactions. A new concept of consistency is proposed to replace it. Possible mechanisms of the acceleration of the transitions by the specific short-range interactions are discussed.

Computers↗
PubMed1979

Studies on protein folding, unfolding and fluctuations by computer simulation. IV. Hydrophobic interactions.

The theoretical model of proteins on the two-dimensional square lattice, introduced previously, is extended to include the hydrophobic interactions. Two proteins, whose native conformations have different folded patterns, are studied. Units in the protein chains are classified into polar units and nonpolar units. If there is a vacant lattice point next to a nonpolar unit, it is interpreted as being occupied by solvent water and the entropy of the system is assumed to decrease by a certain amount. Besides these hydrophobic free energies, the specific long-range interactions studied in previous papers are assumed to be operative in a protein chain. Equilibrium properties of the folding and unfolding transitions of the two proteins are found to be similar, even though one of them was predicted, based on the one globule model of the transitions, to unfold through a significant intermediate state (or at least to show a tendency toward such a behavior), when the hydrophobic interactions are strongly weighted. The failure of this prediction led to the development of a more refined model of transitions; a non-interacting local structure model. The hydrophobic interactions assumed here have a character of non-specific long-range interactions. Because of this character the hydrophobic interactions have the effect of decelerating the folding kinetics. The deceleration effect is less pronounced in one of the two proteins, whose native conformation is stabilized by many pairs of medium-range interactions. It is therefore inferred that the medium-range interactions have the power to cope with the decelerating effect of the non-specific hydrophobic interactions.

Computers↗
PubMed1978

Respective roles of short- and long-range interactions in protein folding.

A lattice model of protein is studied by a Monte Carlo simulation method. The native conformation of the lattice protein molecule is stabilized by specific long-range and short-ranged interactions. By comparing results of simulation for different relative weights of the long- and short-range interactions, it is concluded that the specific long-range interactions are essential for highly cooperative stabilization of the native conformation and that the short-range interactions accelerate the folding and unfolding transitions.

Models, Chemical↗
PubMed1976

Theory of large-amplitude conformational fluctuations in native globular proteins. Independent fluctuating site model.

A theory is developed about large-amplitude conformational fluctuations in globular proteins in their native or predenaturational state. A model is introduced, an independent fluctuating site model, in which we assume that there is more than one independent fluctuating site, each one localized in some part of a protein molecule. Without assuming any further details for each fluctuating site, the entropy S versus enthalpy H curve of this model is shown to be convex. From this fact the predenaturational excess heat capacity can be derived, as observed in recent experimental studies of a few systems of a protein in solution.

Mathematics↗
PubMed1975

Breathing mode of conformational fluctuations in globular proteins.

Globular proteins in the native state are assumed to behave as continuous elastic spheres in the low frequency breathing motions. Reasonable values of Young's modulus E = 10(11) dyne/cm2 and the radius of the sphere ro = 20 A, yield a wave number of 26 cm-1 for the fundamental vibration of the sphere. The peak at around 30 cm-1 in the laser Raman spectra of native alpha-chymotrypsin and pepsin observed by Brown et al. might be assigned to the breathing motion which the native proteins undergo as continuous elastic bodies.

Mathematics↗
PubMed1975

Theory of reversible denaturation of globular proteins.

A theoretical method is developed by which the character of the process of protein denaturation (e.g., whether or not it is of the all-or-none type) can be discussed in terms of conformation of native proteins and the forces stabilizing it. An important role is played by a quantity S(H): entropy of a protein molecule in solution in the conformational states with a given value of enthalpy H. It is demonstrated that the all-or-none type denaturation of proteins is a rather direct consequence of the globularity and specificity of the native conformations. Denaturations with significant intermediate states are discussed. Denaturations induced by added denaturants are also discussed.

Mathematics↗