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Biomedical subjects

K C Chou

Publications and source records attributed to K C Chou.

At least 127 records · Page 7Linked to original sources
PubMed1985

Interactions between an alpha-helix and a beta-sheet. Energetics of alpha/beta packing in proteins.

Conformational energy computations have been carried out to determine the favorable ways of packing a right-handed alpha-helix on a right-twisted antiparallel or parallel beta-sheet. Co-ordinate transformations have been developed to relate the position and orientation of the alpha-helix to the beta-sheet. The packing was investigated for a CH3CO-(L-Ala)16-NHCH3 alpha-helix interacting with five-stranded beta-sheets composed of CH3CO-(L-Val)6-NHCH3 chains. All internal and external variables for both the alpha-helix and the beta-sheet were allowed to change during energy minimization. Four distinct classes of low-energy packing arrangements were found for the alpha-helix interacting with both the parallel and the anti-parallel beta-sheet. The classes differ in the orientation of the axis of the alpha-helix relative to the direction of the strands of the right-twisted beta-sheet. In the class with the most favorable arrangement, the alpha-helix is oriented along the strands of the beta-sheet, as a result of attractive non-bonded side-chain-side-chain interactions along the entire length of the alpha-helix. A class with nearly perpendicular orientation of the helix axis to the strands is also of low energy, because it allows similarly extensive attractive interactions. In the other two classes, the helix is oriented diagonally relative to the strands of the beta-sheet. In one of them, it interacts with the convex surface near the middle of the saddle-shaped twisted beta-sheet. In the other, it is oriented along the concave diagonal of the beta-sheet and, therefore, it interacts only with the corner regions of the sheet, so that this packing is energetically less favorable. The packing arrangements involving an antiparallel and a parallel beta-sheet are generally similar, although the antiparallel beta-sheet has been found to be more flexible. The major features of 163 observed alpha/beta packing arrangements in 37 proteins are accounted for in terms of the computed structural preferences. The energetically most favored packing arrangement is similar to the right-handed beta alpha beta crossover structure that is observed in proteins; thus, the preference for this connectivity arises in large measure from this energetically favorable interaction.

Alanine↗
PubMed1985

The biological functions of low-frequency vibrations (phonons) 5. A phenomenological theory.

Low-frequency internal motions of a biomacromolecule are thought to possess significant biological function from the dynamic point of view. In this paper, a general phenomenological theory is established by which it is clearly verified that low-frequency resonance plays a central role in the energy transmission required during the cooperative interaction between subunits in a protein oligomer. According to the present theory, it is found that the energy transmission between a pair of diagonal subunits in a protein oligomer with a polygon arrangement is the most efficient, so as to in a sense further predict that after a ligand is bound to a subunit by random collision, its diagonal subunit in the same protein oligomer will possess the greatest probability of binding with the next ligand. Furthermore, based on the concept of the 'resonance-controlled trigger' derived from the phenomenological theory, it is feasible to estimate the lower time limit of allosteric transition from one subunit to the other. Such a time limit depends on the dominant low-frequency mode of each subunit, the ratio of the coupling force constant to the corresponding inherent force constant, as well as the geometrical arrangement of subunits in a protein oligomer. So far none of the allosteric transitions observed in proteins has exceeded the time limit as defined here, indicating a logical consistency between our theory and the experiments.

Energy Transfer↗
PubMed1985

Low-frequency motions in protein molecules. Beta-sheet and beta-barrel.

Low-frequency internal motions in protein molecules play a key role in biological functions. Based on previous work with alpha-helical structure, the quasi-continuum model is extended to the beta-structure, another fundamental element in protein molecules. In terms of the equations derived here, one can easily calculate the low-frequency wave number of a beta-sheet in an accordionlike motion, and the low-frequency wave number of a beta-barrel in a breathing motion. The calculated results for immunoglobulin G and concanavalin A agree well with the observations. These findings further verify that the observed low-frequency motion (or the so-called dominant low-frequency mode) in a protein molecule is essentially governed by the collective fluctuations of its weak bonds, especially hydrogen bonds, and the internal displacement of the massive atoms therein, as described by the quasi-continuum model.

Kinetics↗
PubMed1984

Low-frequency vibrations of DNA molecules.

A model for calculating the low-frequency modes in DNA molecules is presented. The present model is associated with the 'breathing' of a DNA molecule as well as its complementary hydrogen bonds. The calculated results show excellent agreement with the observed low-frequency wavenumber (30 cm-1). Consequently, such an internal motion as reflected in the proposed model might be the origin of the observed low-frequency vibration in DNA molecules. This is helpful for investigating the relevant biological functions, which so far have been discussed by many scientists.

Base Composition↗
PubMed1984

The biological functions of low-frequency vibrations (phonons). 4. Resonance effects and allosteric transition.

Based on the internal structure of oligoprotein as well as the basic physical characteristics+ of vibrations, it is deduced that the low-frequency vibrations possess some exceptional functions in transmitting biological information at the molecular level. In particular, according to the viewpoint of energy exchange and intramolecular displacement, it is demonstrated that the low-frequency resonance plays a very significant role during the dynamic process of allosterism of an oligomeric protein molecule. Furthermore, the cooperative reaction between hemoglobins and ligands is taken as an example, through which it is seen that some observed phenomena, whose dynamic principle has thus far been unclear, can be explicitly interpreted in terms of the concept of low-frequency resonance.

Allosteric Regulation↗
PubMed1984

Biological functions of low-frequency vibrations (phonons). III. Helical structures and microenvironment.

Low-frequency vibrations in biomacromolecules possess significant biological functions. In this paper, the alpha-helix element is compared with a mass-distributed spring. Based on this, a set of intuitive and easily handled equations are derived for predicting the fundamental frequencies of helical structures in protein molecules. As shown in the equations, the fundamental frequency depends not only on the constituents of a helix itself but also on its microenvironment. The calculated results agree with the observations. The calculations also demonstrate that the low-frequency vibrations with wave number of approximately 30 cm-1 do not necessarily arise from motions that involve either all or very large portions of the protein molecule as previously thought; a piece of helix containing more than 10 residues and surrounded by a proper microenvironment can also generate such low-frequency motions. Furthermore , we illustrate that the low-frequency motions are closely related to the native state of a protein molecule. Upon denaturation, which is accompanied by a radical change of the relevant microenvironment, the original fundamental frequency also disappears. Consequently, this kind of special frequency termed activating low frequency can serve as a dynamic criterion in identifying whether a biomacromolecule is in its native state. The energy of a phonon excited by this kind of low-frequency vibration is of the same order of magnitude as the average enthalpy value per residue measured during conformational change in some protein molecules. Therefore, there must be some intrinsic relation between the allosteric transitions of protein molecules and their low-frequency motions.

Biophysical Phenomena↗
PubMed1983

Identification of low-frequency modes in protein molecules.

It is demonstrated that the observed low-frequency motions with wave numbers of 22 cm-1 and 25 cm-1 for insulin and lysozyme respectively originate from the accordion-like motions of the principal helices therein. The calculated results based on such a model are in good agreement with the observed values. During calculations the role of the internal microenvironment upon the low-frequency motion is naturally revealed, so as to elucidate as well why this kind of low-frequency motion is so sensitive to the conformations of proteins observed.

Insulin↗
PubMed1983

Role of interchain interactions in the stabilization of the right-handed twist of beta-sheets.

Conformational energy computations have been carried out for parallel and antiparallel beta-sheets composed of poly-L-Val and poly-L-Ile peptide chains, each consisting of four and of six residues, respectively, with CH3CO- and-NHCH3 end groups. The beta-sheets considered contained three and five equivalent chains, respectively. All computed minimum-energy beta-sheets were found to have a large right-handed twist of a magnitude that corresponds to the mean twist of beta-sheets observed in globular proteins. The twist has the same sign but is much larger than in beta-sheets of poly-L-Ala, because of intra- and interchain interactions between the bulky beta-branched side-chains. While the right-handed twist is a result of intrachain interactions between side-chains in the case of poly-L-Val, these interactions would favor a left-handed twist in poly-L-Ile, and the right-handed twist in the latter is a result of interchain interactions. Parallel beta-sheets are more stable than antiparallel sheets for both poly-L-Val and poly-L-Ile, in contrast to poly-L-Ala. This result agrees with observations on the preferred orientation of the chains in oligopeptides that form beta-structures. It also explains the observed high relative frequencies of occurrence of Val and Ile residues in parallel beta-sheets, as compared with antiparallel sheets, in globular proteins.

Hydrogen Bonding↗
PubMed1983

Low-frequency vibrations of helical structures in protein molecules.

A physically intuitive and mathematically easily handled formula is presented for calculating the low-frequency vibrations of helical structures in protein molecules. alpha-Chymotrypsin is taken as an example, and the calculated result shows precise agreement with observations of the low-frequency Raman spectra. As reflected in the formula, this kind of low frequency is very sensitive to the conformation of a biomacromolecule, and can therefore serve as a vehicle to investigate the mechanism of action of a biomacromolecule from the viewpoint of dynamics. On this basis a feasible experiment is suggested by which one can examine the relationship between a presumed mode of low-frequency vibration in a biomacromolecule and its activity.

Chymotrypsin↗
PubMed1982

A thermal-variation method for analysing the rate constants of the Michaelis--Menten mechanism.

By analysing the variations of saturation velocity and Michaelis constant with temperature and invoking the mathematical constraint represented by the Arrhenius equation, it becomes possible to estimate k+2 and indistinguishably k+1 and k-1 for the Michaelis--Menten mechanism of one-substrate enzyme reactions. Distinction between k+1 and k-1 may be obtained through the determination of isotopic rate effects. This procedure thus provides a basis for evaluating all three rate constants of the one-substrate mechanism, and disproves the suggestion that k+1 and k-1 are intrinsically unobtainable from steady-state kinetic measurements.

Enzymes↗
PubMed1982

Origin of the right-handed twist of beta-sheets of poly(LVal) chains.

The energies of three- and five-chain antiparallel and parallel beta-sheets were minimized. Each chain consisted of six L-valine residues with CH3CO and NHCH3 end groups; the chains were considered to be equivalent, but all dihedral angles of a given chain were allowed to vary independently during energy minimization. The minimum-energy structures had a considerable right-handed twist, as observed in globular proteins. This right-handed twist is due primarily to intrachain nonbonded interactions. Such interactions between the C gamma 1H3 group of the ith residue and the C gamma 2H3 group of the (i + 2)th residue of the same chain favor a twist of either handedness over the flat structure. However, many small intrastrand pair-wise interatomic interactions involving the C gamma 1H3 and C gamma 2H3 groups, especially the interactions of these groups with the O and amide H atoms of the neighboring peptide groups, make the right-handed twisted structure energetically more favorable than the left-handed one. The intrastrand side-chain torsional energy plays a small additional role in favoring the right-twisted structure over both the flat and the left-twisted structures. The interstrand interactions favor flat structures, but they are not strong enough to overcome the intrastrand interactions that favor the twisted structure; they only decrease somewhat the extent of the right-handed twist of the beta-sheets.

Calorimetry↗
PubMed1981

The flexibility during the juxtaposition of reacting groups and the upper limits of enzyme reactions.

The combination between enzymes and substrates occur only after their reacting groups are in juxtaposition with each other. This will greatly reduce the probability of their effective encounters. However, the results calculated with the finite elements method show that the reaction limits will not decrease substantially if van der Waal's forces and a reasonable flexibility during such a juxtaposition are taken into account.

Binding Sites↗
PubMed1981

A new graphical rule for rate laws of enzyme reactions with branched pathways.

A new graphical rule is presented for deriving the rate equations of enzyme reactions. The new rule has the following advantages: (i) it is very effective in simplifying the calculations for complex mechanisms, especially for those with branched pathways; (ii) a significant and intuitive correlation between the rule and the mechanism is established through the product-releasing cycle and product-combining cycle.

Chemical Phenomena↗