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Biomedical subjects

L B Kier

Publications and source records attributed to L B Kier.

At least 19 recordsLinked to original sources
PubMed2001

Issues in representation of molecular structure the development of molecular connectivity.

Significant issues in the representation of molecular structure and the development of the molecular connectivity paradigm are presented. In the molecular connectivity paradigm, molecular structure is represented directly. Kier and Hall developed the method by creating ways to encode electronic information based on the paradigm developed from the Randić branching index. The simple and valence delta values were created to encode atomic and valence-state electronic information through counts of sigma, pi, and lone pair electrons. A family of indices was created to provide a wide range of structure information. The key aspects of the development are presented and discussed in such a way as to reveal, at least in part, the imaginative thinking involved in the process. Possible future roles for molecular connectivity chi indices are discussed.

Algorithms↗
PubMed2001

Molecular connectivity: intermolecular accessibility and encounter simulation.

The simple molecular connectivity indices are interpreted as summations of bond accessibilities to bimolecular encounters with another, identical molecule. To transcend this model, a molecule is treated as disjecta membra with each bond modeled as a discrete cell in a dynamic simulation of many molecules. Each bond accessibility is transformed into a cellular automata rule. The dynamics are run for each of 38 alkanes, recording the average number of cell encounters, beta. The beta values show a high correlation with the boiling points. The significance of the bond accessibilities and the concept of intermolecular encounters explaining the molecular connectivity indices is supported by these findings.

Alkanes↗
PubMed2001

Database organization and searching with E-State indices.

The electrotopological state (E-State) and its extension, the atom-type E-State, is presented as a representation of atom and molecular fragment structure useful for chemical database organization and management. An approach to database organization, using substituted esters and benzene derivatives as examples, reveals the descriptive power of the E-State paradigm. With a database, organized on the basis of structural relationships as described here, it is possible to search for similar molecular structures with potential for comparable activity. The searches using the atom-type E-State indices are demonstrated with several examples.

Benzene↗
PubMed2000

A cellular automata model of chromatography.

Dynamic models of the behavior of solvent and solute molecules can be made using cellular automata. A chromatographic column was represented by use of a cellular automata grid of 43 x 200 spaces. Solvent (mobile phase), solute and stationary phase cells were designated to simulate the chromatographic situation. The movements of solute and solvent cells down the grid were monitored for different numbers of iterations, different flow rates and different affinities of the solutes for the stationary phase and the solvent for itself. The cellular automata dynamics were successfully able to model expected chromatographic behavior except in a few cases where the number of cells was not large enough to provide an average value reflective of the molecular situation.

Cell Separation↗
PubMed2000

A cellular automata model of an anticipatory system.

An anticipatory system has been modeled using the dynamic characteristics of cellular automata. Rules governing the steps in an enzymatic conversion of substrates to products are operative in the system. A concentration of an intermediate product influences the creation of a supplemental enzyme that enhances the competence of an enzyme down stream. This anticipation of the future event creates a condition in which the concentration of a later substrate is suppressed, a property characteristic of the system. The model presents a useful opportunity to study a variety of aspects of this fascinating phenomena.

Computer Simulation↗
PubMed2000

Cellular automata models of chemical systems.

This paper describes the use of kinematic, asynchronous, stochastic cellular automata to model liquid properties, solution phenomena and kinetic phenomena encountered in complex biological systems. Cellular automata models of dynamic phenomena represent in silico experiments designed to assess the effects of competing factors on the physical and chemical properties of solutions and other complex systems. Specific applications include solution behavior, separation of immiscible liquids, micelle formation, diffusion, membrane passage, first- and second-order chemical kinetics, enzyme activity and acid dissociation. Cellular automata is thus considered as providing an exploratory method for the analysis of dynamic phenomena and the discovery and understanding of new, unexpected phenomena.

Animals↗
PubMed1998

QSAR modeling with the electrotopological state indices: corticosteroids.

A structure-activity analysis of a series of steroids binding to corticosteroid-binding globulin was made using the electrotopological state index for each atom in the molecule. Two indices were found to correlate well with the binding affinity. The indices encode structural characteristics in the A and the D rings of the steroids in the study. One of the indices was formulated as the difference between two indices in the A ring. The two were not intercorrelated, suggesting that the composite index signals the influence of structure changes in or near the A ring that can be monitored by the composite index. This is a new observation using this structure-activity method. It is suggested that this model makes some contributions towards detection of the pharmacophore.

Adrenal Cortex Hormones↗
PubMed1997

A cellular automata model of diffusion in aqueous systems.

A cellular automata model of a solute diffusing in water has been created and studied for the influential attributes. The results with this model are in agreement with experimental results; that is, that lipophilic solutes diffuse faster than do polar solutes. The model reveals that a solution composed of a relatively lipophilic solute permits a greater extent of diffusion of another solute. This observation is in agreement with the model showing a diffusion preference of a solute between two solutions made up of differing polarities. The solute diffuses farther into the lipophilic solution. A temperature-lipophilicity phase diagram shows the influence of these two attributes on the rate of diffusion. A model of diffusion through solutions containing stationary ingredients reveals a faster rate when the ingredient is lipophilic. We are led to a conclusion that the relative lipophilicity of solutes or stationary ingredients in a solution has a direct influence on the rates of diffusion of other solutes in their midst.

Diffusion↗
PubMed1996

E-state fields: applications to 3D QSAR.

The derivation of a new 3D QSAR field based on the electrotopological state (E-state) formalism is described. A complementary index and its associated field, the HE-state, describing the polarity of hydrogens is also defined. These new fields are constructed from a nonempirical index that incorporates electronegativity, the inductive influence of neighboring atoms, and the topological state into a single atomistic descriptor. The classic CoMFA steroid test data set was examined with models incorporating the E-state and HE-state fields alone and in combination with steric, electrostatic and hydropathic fields. The single best model was the E-state/HE-state combination with q2 = 0.803 (three components) and r2 = 0.979. Using the E-state and/or HE-state fields with other fields consistently produced models with improved statistics, where the E-state fields provided a significant, if not dominant, contribution.

Binding Sites↗
PubMed1996

A cellular automata model of enzyme kinetics.

We have developed a cellular automata model of an enzyme reaction with a substrate in water. The model produces Michaelis-Menten kinetics with good Lineweaver-Burk plots. The variation in affinity parameters predicts that, in general, hydrophobic substrates are more reactive with enzymes, this attribute being more important than the relationship between enzyme and substrate. The ease of generation and the illustrative value of the model lead us to believe that cellular automata models have a useful role in the study of dynamic phenomena such as enzyme kinetics.

Automation↗
PubMed1995

A cellular automata model of the hydrophobic effect.

Dynamic simulations of solute molecules in water are made using cellular automata. By varying the parameter governing the breaking probability of water-solute tesselated pairs, sets of configurations were modeled of solutions ranging from polar to non-polar solutes. The emergent behavior of the non-polar solute models leads us to believe that this is a possible model of the hydrophobic effect.

Models, Chemical↗
PubMed1992

A quantitative structure-activity relationship (QSAR) study of alkylpyrazine odor modalities.

The odor strength of a series of alkylpyrazines has been quantitatively investigated applying molecular connectivity, molecular shape, and the recently developed electrotopological state indices. The successful use of the latter parameters indicates that both electronic and topological features contribute to the odor strength of the compounds under study, while the specific role of the two nitrogen atoms is revealed.

Chemical Phenomena↗
PubMed1991

The concept of molecular structure in structure-activity relationship studies and drug design.

We can justify the use of any model, method, or algorithm if we clearly state our goals, understand the basis of our procedures, and fully appreciate the true nature and limitations of the results. As we have illustrated here, the creation of new wisdom may appear to be a consequence of our labors. There are cases, however, where this creation may be only an illusion. In any analysis of structure-activity, property-activity, or structure-property relationships, the degree of understanding of the nature of the starting data therefore determines the level of confidence ascribable to any result and prediction. This is, in essence, the message of our inquisitive meditations on the deep nature of structure-activity relationships.

Chemistry, Pharmaceutical↗
PubMed1990

An electrotopological-state index for atoms in molecules.

A new method for molecular structure description is presented in which both electronic and topological characteristics are combined. The method makes use of the hydrogen-suppressed graph to represent the structure. The focus of the method is on the individual atoms and hydride groups of the molecular skeleton. An intrinsic atom value is assigned to each atom as I = (delta v + 1)/delta, in which delta v and delta are the counts of valence and sigma electrons of atoms associated with the molecular skeleton. The electrotopological-state value, Si, for skeletal atom i is defined as Si = Ii + delta Ii, for second row atoms, where the influence of atom j on atom i, delta Ii, is given as sigma(Ii-Ij)/rij2; rij is the graph separation between atom i and atom j, counted as the number of atoms. The characteristics of the electrotopological state values are indicated by examples of various types of organic structures, including chain lengthening, branching, heteroatoms, and unsaturation. The relation of the E-state value to NMR chemical shift is investigated for a series of alkyl ethers. The E-state oxygen value gives an excellent correlation with the 17O NMR: r = 0.993 for 10 ethers. A biological application of the E-state values in QSAR analysis is given for the binding of barbiturates to beta-cyclodextrin.

Barbiturates↗
PubMed1989

Differential molecular connectivity in data-base fragment searching.

A general scheme is described in which molecular fragments are coded from molecular connectivity values. Specifically a fragment is described by the difference between a simple connectivity index of a certain order and the valence connectivity index of the same order. This numerical value is then used to search for that particular fragment among stored fragment values associated with a molecular connectivity calculation. Examples illustrate the method.

Chemical Phenomena↗