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R Rein

Publications and source records attributed to R Rein.

At least 55 records · Page 3Linked to original sources
PubMed1987

Geometrical analysis of Cys-Cys bridges in proteins and their prediction from incomplete structural information.

Analysis of C-alpha atom positions from cysteines involved in disulphide bridges in protein crystals shows that their geometric characteristics are unique with respect to other Cys-Cys, non-bridging pairs. They may be used for predicting disulphide connections in incompletely determined protein structures, such as low resolution crystallography or theoretical folding experiments. The basic unit for analysis and prediction is the 3 x 3 distance matrix for Cx positions of residues (i - 1), Cys(i), (i +1) with (j - 1), Cys(j), (j + 1). In each of its columns, row and diagonal vector--outer distances are larger than the central distance. This analysis is compared with some analytical models.

Algorithms↗
PubMed1987

Computer modeling of the neurotoxin binding site of acetylcholine receptor spanning residues 185 through 196.

A model of the complex between the acetylcholine receptor and the snake neurotoxin, cobratoxin, was built by molecular model building and energy optimization techniques. The experimentally identified functionally important residues of cobratoxin and the dodecapeptide corresponding to the residues 185-196 of acetylcholine receptor alpha subunit were used to build the model. Both cis and trans conformers of cyclic L-cystine portion of the dodecapeptide were examined. Binding residues independently identified on cobratoxin are shown to interact with the dodecapeptide AChR model.

Amino Acid Sequence↗
PubMed1987

Interaction scheme of the binding of acetylcholine receptor with cobratoxin and erabutoxin.

Snake toxins bind to the periphery of acetylcholine receptor which overlaps with the agonist site, thus inhibiting the ion channel opening mechanism. It has been proposed (Stroud and Finer-Moore, 1985) that the residues lying between Cys 130 and Cys 142 of the alpha-subunit of the acetylcholine receptor participate in the binding of toxins. A three-dimensional model of acetylcholine with cobratoxin and erabutoxin is built based on the interaction scheme proposed by Smart et al. (1984). The differences in the hydrogen bonding schemes between the two complexes are discussed. The results show the effect of the conservative substitution (Asp/Glu) at position 42 in the toxins on the binding interactions.

Animals↗
PubMed1986

Multistep modeling (MSM) of biomolecular structure application to the A-G mispair in the B-DNA environment.

A multistep modeling procedure has been evolved to study the structural changes introduced by lesions in DNA. We report here the change in the structure of regular B-DNA geometry due to the incorporation of Ganti-Aanti mispair in place of a regular G-C pair, preserving the helix continuity. The energetics of the structure so obtained is compared with the Ganti-Asyn configuration under similar constrained conditions. We present the methodology adopted and discuss the results.

Computer Graphics↗
PubMed1986

Multistep modeling of protein structure: application to bungarotoxin.

Modelling of bungarotoxin in atomic details is presented in this article. The model-building procedure utilizes the low-resolution crystal coordinates of the c-alpha atoms of bungarotoxin, sequence homology within the neurotoxin family, as well as high-resolution x-ray diffraction data of cobratoxin and erabutoxin. Our model-building procedure involves: (a) principles of comparative modelling, (b) embedding procedures of distance geometry, and (c) use of molecular mechanics for optimizing packing. The model is not only consistent with the c-alpha coordinates of crystal structure, but also agrees with solution conformational features of the triple-stranded beta sheet as observed by NOE measurements.

Bungarotoxins↗
PubMed1986

An improved approach to the analysis of drug-protein binding by distance geometry.

The calculation of side chain centers of coordinates and the subsequent generation of side chain-side chain and side chain-backbone distance matrices is suggested as an improved method for viewing interactions inside proteins and for the comparison of protein structures. The use of side chain distance matrices is demonstrated with free PTI, and the use of difference distance matrices for side chains is shown for free and trypsin-bound PTI as well as for the X-ray structures of trypsin complexes with PTI and with benzamidine. It is found that conformational variations are reflected in the side chain distance matrices much more than in the standard C-C distance representations.

Benzamidines↗
PubMed1986

Rational design and application of idiotope vaccines.

Current emphasis on risk factors associated with established vaccines and pressing needs for vaccines against certain viral transmitted diseases have stimulated the search for new conceptual and practical approaches to vaccine production. Among these developments, the idiotope vaccine method has produced promising results. In this review the basic and conceptual principles for idiotype vaccine design are discussed. A novel approach for identifying idiotopic structures in the three dimensional structure of internal idiotope antigens is developed. The method is based on the relationship of the immune response with the evolutionary variation and diversity of the immunoglobulin family. Idiotopic structures are found in specialized topographic regions on the surface of the immunoglobulin molecule. The knowledge of these idiotope domains will facilitate the synthesis of idiotope expressing peptides and the computer modeling of the three dimensional structure of internal idiotope antigens. Finally, the existing evidence for successful application of the idiotope vaccine method is summarized and new disease groups are identified which could benefit from the development of idiotope vaccines.

Autoimmune Diseases↗
PubMed1985

Potential-derived point-charge model study of electrostatic interaction energies in some hydrogen-bonded systems.

Mulliken's atomic changes (MC) and potential derived (PD) point charges obtained from STO-3G wave functions are used to study the electrostatic interaction energies for a series of representative hydrogen-bonded complexes. The results of the above-mentioned models are compared with the more accurate results of segmental multipole moment (SMM) expansion, and it is shown that the PD model is superior to the MC model. The results of PD model are shown to be well correlated with the results of SMM expansion technique. Results of our calculations using 6-31G and 6-31G** PD charges are also reported here. Electrostatic interaction energies obtained using 6-31G** PD charges are compared with the 6-31G** SCF interaction energies available for the nine hydrogen-bonded dimers of ammonia, water, and hydrogen fluoride and a good correlation between the two is shown. The interrelationship between the results of different basis sets are also examined for the PD point-charge model. The electrostatic interaction energies obtained using STO-3G PD model are shown to be well correlated to the results of 6-31G and 6-31G** PD models.

Ammonia↗
PubMed1984

Potential-derived point-charge model study of electrostatic interactions in DNA base components.

Ab initio electrostatic potentials obtained using STO-3G wavefunctions for guanine, cytosine, adenine, and thymine are used to calculate potential-derived (PD) point charges for these base components. Calculated PD point charges are used to estimate the electrostatic contributions to hydrogen-bonding and stacking interaction energies of ten sequence isomers of B-DNA. These estimates are in excellent agreement with the results of the more elaborate segmental multipole moment expansion technique.

Adenine↗
PubMed1984

Potential derived point charge model study of electrostatic interaction energies in some complexes of water with uracil, thymine, and cytosine.

Potential derived (PD) point charges and segmental multipole moments are calculated for water, uracil, thymine, and cytosine using STO-3G quality wave functions. The PD point charges are used to estimate the electrostatic interaction energies for a series of complexes of water with these nucleic acid bases. It is shown here that the results obtained using simple PD charge model is very similar to those obtained from more elaborate segmental multipole moment analysis.

Algorithms↗
PubMed1983

Molecular modelling of protein-nucleic acid interactions.

Computer modeling techniques to study the interaction of proteins with nucleic acids are presented. The methods utilize information from genetic and chemical modification experiments and macromolecular structural constraints. These techniques, in addition to computer model building procedures and theoretical energy calculations, are illustrated for the study of the lac and cro repressor-operator systems. Our predicted interactions between lac and its operator agree with those recently reported for lac based upon sequence alignment with the cro repressor. Several molecular models of the putative helical segment of cro interacting with its OR3 operator are presented. These models are reflective of intermediate conformations experienced by the repressor in recognition of the operator sequence. The results of our studies are further discussed in terms of the design of short peptides interacting with nucleic acid sequences and the evolutionary requirements in establishing these repressor interactions.

Amino Acid Sequence↗
PubMed1982

dnaC-dependent reconstitution of replication forks in Escherichia coli lysates.

Lysates of Escherichia coli exhibit a DNA-synthesizing activity that depends on the presence of replication forks and of replication proteins. Replicative activity was reconstituted in vitro by mixing lysates prepared from temperature-sensitive dnaB mutants with wild-type dnaB protein. Lysates of double mutants deficient in both dnaB and dnaC genes could only be complemented by the addition of both dnaB and dnaC proteins, whereas lysates deficient in dnaC protein did not require the addition of any exogenous factor. This shows that the replication machinery, once it is running along the chromosome, is independent of dnaC protein, dnaC activity, however, is required for the replacement of defective dnaB protein at running replication forks.

Bacterial Proteins↗
PubMed1980

Molecular models of induced DNA premutational damage and mutational pathways for the carcinogen 4-nitroquinoline 1-oxide and its metabolites.

The carcinogen 4-nitroquinoline 1-oxide (4NQO) and its metabolites undergo intercalative or covalent binding with DNA. Recent evidence indicates that the latter binding pattern is probably facilitated by an initial weaker intercalative interaction that can align potentially reactive sites on a 4NQO-metabolite and adjacent stacked bases. In the present study, we have proposed numerous possible covalent reaction products between 4NQO and its metabolites with DNA mini-helices based on chemical properties and key 'short-contacts' after energy-minimization in 21 different intercalative-like complexes. It is known from numerous experimental studies that 90% of the quinoline-bound DNAs in vivo involve guanine with the remaining 10% apparently involving adenine residues. The results of the present study suggest that this trend is not due to the greater affinity of the quinolines for guanine, but instead results from secondary processes involving the preferential formation of apurinic sites at aralkyl-adenine residues over that of aralkyl-guanine residues. In addition, observed mutational patterns can be rationalized in terms of the proposed reaction-products. The role of DNA repair mechanisms in the removal and correction of the different proposed reaction products are discussed. The binding pattern of several other aromatic carcinogens are similar to those depicted in the present work for the 4NQO-metabolites; hence the present study may be of some general significance.

4-Nitroquinoline-1-oxide↗
PubMed1980

A program for the computation of helical parameters from internal coordinates.

A method for the calculation of helical parameters from internal coordinates of an arbitrary repeat unit, has been implemented in a FORTRAN IV program. The coordinates of all atoms in a cylindrical coordinate system are also obtained. An application of the program for a systematic approach to the problem of protein-DNA recognition is introduced.

Computers↗