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Biomedical subjects

D Perahia

Publications and source records attributed to D Perahia.

At least 37 records · Page 2Linked to original sources
PubMed1986

Interdomain motion in liver alcohol dehydrogenase. Structural and energetic analysis of the hinge bending mode.

A study of the hinge bending mode in the enzyme liver alcohol dehydrogenase is made by use of empirical energy functions. The enzyme is a dimer, with each monomer composed of a coenzyme binding domain and a catalytic domain with a large cleft between the two. Superposition of the apoenzyme and holoenzyme crystal structures is used to determine a rigid rotation axis for closing of the cleft. It is shown that a rigid body transformation of the apoenzyme to the holoenzyme structure corresponds to a 10 degrees rotation of the catalytic domain about this axis. The rotation is not along the least-motion path for closing of the cleft but instead corresponds to the catalytic domain coming closer to the coenzyme binding domain by a sliding motion. Estimation of the energy associated with the interdomain motion of the apoenzyme over a range of 90 degrees (-40 to 50 degrees, where 0 degrees corresponds to the minimized crystal structure) demonstrates that local structural relaxation makes possible large-scale rotations with relatively small energy increments. A variety of structural rearrangements associated with the domain motion are characterized. They involve the hinge region residues that provide the covalent connections between the two domains and certain loop regions that are brought into contact by the rotation. Differences between the energy minimized and the holoenzyme structures point to the existence of alternative conformations for loops and to the importance of the ligands in the structural rearrangements.

Alcohol Dehydrogenase↗
PubMed1982

Molecular dynamics of an alpha-helical polypeptide: Temperature dependence and deviation from harmonic behavior.

The mean square amplitudes of atomic fluctuations for a polypeptide (decaglycine) alpha-helix evaluated from molecular dynamics simulations at seven temperatures between 5 and 300 K are compared with analytic harmonic results and with experimental values. Above 100 K the harmonic approximation significantly underestimates the amplitudes of the displacements. Analysis of the time dependence of the fluctuations shows that low-frequency modes (<75 cm(-1)) dominate the atomic fluctuations and that there is a contribution with a very long relaxation time (>10 ps). Quantum corrections to the amplitude of the fluctuations are found to be small above 50 K. The mean square amplitudes obtained from the molecular dynamics simulations are compared with the values derived from x-ray temperature (Debye-Waller) factors for metmyoglobin (80, 250, and 300 K) and ferrocytochrome c (300 K).

Journal Article↗
PubMed1979

The molecular electrostatic potential of the B-DNA helix. VI. The regions of the base pairs in poly (dG.dC) and poly (dA.dT).

The evaluation of the electrostatic molecular potential at important nucleophilic sites of the purine and pyrimidine bases in poly (dG.dC) and poly (dA.dT) and of the evolution of the potential through the series free bases-nucleosides-nucleotides-single polynucleotide helices-double helices enables the interpretation of the evolution of the corresponding reactivity of the bases towards a series of electrophilic carcinogenic and mutagenic reactants.

Base Composition↗
PubMed1978

Molecular orbital studies on the conformations of 8-amino- and 8-dimethylaminoadenosine 5'-monophosphate.

The quantum mechanical PCILO method has been applied for the determination of conformational properties of 8-amino- and 8-dimethylaminoadenosine 5'-monophosphate. Contrary to other 8-substituted nucleotides the amino derivative shows a preference for an anti arrangement about the glycosidic bond. This conformation is stabilized by an intramolecular hydrogen bond between the purine and the exocyclic group. 8-dimethylamino-adenosine-5'-monophosphate adopts the syn conformation with slightly rotated dimethylamino group. There is, however, a local minimum for the anti form associated with the unusual value of chiCN = 300 degrees. This minimum is probably populated when the nucleotide is bound to lactate dehydrogenase apoenzyme. No particularly strong interactions are necessary for the stabilization of the anti form. The computations account satisfactorily for the available experimental data.

Adenosine↗
PubMed1977

A molecular orbital investigation of the conformation of transfer RNA.

The PCILO method has been used for a theoretical exploration of the conformational properties of tRNAPhe with respect to the phosphodiester torsion angles. The computations were based on the utilisation of the dinucleoside triphosphate model and took into account the different combinations of sugar puckers and different conformations about the C4'-C5' bond. The dependence of the (omega'-omega) conformational energy maps upon these factors was specified. A detailed comparison is carried out between the theoretical results and experimental data on the crystal structure of tRNAPhe produced by four different groups of investigators.

Computers↗
PubMed1977

Molecular orbital studies on the conformation of the phosphopantetheine moiety of coenzyme A.

Conformational study on phosphopantetheine shows that this compound has an intrinsic tendency to adopt a multitude of conformations which contain hydrogen bonds involving the sulphydryl, hydroxyl, carbonyl and amide groups. The sulphydryl group may form a hydrogen bond with the C(7') = 0 carbonyl group, the latter being also involved in hydrogen bonding with the N(4')-H GROUP. All these hydrogen bondings occur for different conformations around the backbone. The N(7')-H and C(4') = 0 groups are not involved in hydrogen bonding. It is also found that a strong interaction occurs between N(4')-H and 0-3' which is responsible for a rigid conformation around the C(3')-C(4') and C(3')-0(3') bonds. As far as the phosphate group is concerned the results show that this group may interact with the 0(3')-H hydroxyl group to form hydrogen-bonded rings of different sizes. A six-membered ring formed by hydrogen bonding between 0(3')-H and 0-1' appears more favorable than an eight-membered ring involving an anionic oxygen instead of an ester oxygen related to the phosphate group.

Coenzyme A↗
PubMed1977

Theoretical study of the hydration of B-DNA.

A theoretical study of the hydration of the B-form of DNA has been carried out using empirical potential energy functions. In the first stage the hydration scheme of a model compound representing the B-DNA has been determined and the results have been shown to agree to a large extent with those of refined ab initio SCF computations. In the second stage, the stabilization energy due to the presence of water in the first hydration shell was computed by considering the hydrated helix as a supermolecule. The computations indicate appreciable stabilization. The different components contributing to the overall stabilization are determined and analysed.

Binding Sites↗
PubMed1976

Molecular orbital calculations on the conformation of phosphodiesters. An extended correlation between the geometry and the conformation of the phosphate group.

An extension of our previous correlation (C.R. Acad. Sci. Paris, Ser. D (1973) 277, 2257; Biochim. Biophys. Acta (1974) 340, 299) between the geometry of the phosphate group and the conformation of phosphodiesters established by PCILO computations, shows that the probability of gauche-trans or trans-gauche conformations should become appreciable for low values (100-101) of the 33'-P-O5', angle and may even become predominant when the C-O-P angles have also a low value (congruent to 117 degrees). The results agree satisfactorily with available X-ray crystallographic data.

Calorimetry↗