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Biomedical subjects

I Cosic

Publications and source records attributed to I Cosic.

16 recordsLinked to original sources
PubMed2000

The resonant recognition model (RRM) predicts amino acid residues in highly conserved regions of the hormone prolactin (PRL).

The resonant recognition model (RRM) is a model which treats the protein sequence as a discrete signal. It has been shown previously that certain periodicities (frequencies) in this signal characterise protein biological function. The RRM was employed to determine the characteristic frequencies of the hormone prolactin (PRL), and to identify amino acids ('hot spots') mostly contributing to these frequencies and thus proposed to mostly contribute to the biological function. The predicted 'hot spot' amino acids, Phe-19, Ser-26, Ser-33, Phe-37, Phe-40, Gly-47, Gly-49, Phe-50, Ser-61, Gly-129, Arg-176, Arg-177, Cys-191 and Arg-192 are found in the highly conserved amino-terminal and C-terminus regions of PRL. Our predictions agree with previous experimentally tested residues by site-direct mutagenesis and photoaffinity labelling.

Algorithms↗
PubMed1998

Investigations into the cross-reactivity of rabbit antibodies raised against nonhomologous pairs of synthetic peptides derived from HIV-1 gp120 proteins.

The immunological cross-reactivity of several peptides with specific pattern-property characteristics related to the epitopes of human immunodeficiency virus type 1 (HIV-1) gp160/ 120 envelope proteins has been investigated. Proteins with similar primary structures can be expected to show functional or topographic similarities, such as specific epitopes which may cross-react with antibodies derived from the immunisation of animals with other members of the same protein family. These structure-function characteristics may be revealed as periodicities derived from presentations based on the discrete Fourier transformation of the distributions of various physico-chemical amino acid descriptors, constituting the polypeptide backbone and amino acid side-chains of the protein molecule. Such approaches, for example, have permitted prediction of periodicities corresponding to secondary structural motifs, including amphipathic alpha-helices and beta-sheets, within protein sequences, and have helped to clarify potential binding sites for ligands, substrates or cofactors with interacting macromolecules. Based on this approach, characteristic periodicities have been identified which represent common Fourier transform spectral properties of the envelope (ENV) gp160/120 glycoproteins from a range of HIV-1 isolates. In addition, similar periodicities have been detected as components of the discrete Fourier transform representation of the corresponding amino acid descriptors of the CD4 binding domain of gp120. Accordingly, we have synthesised several peptides having periodic characteristics in their discrete Fourier transform representations similar to these HIV-1 proteins. These nonhomologous synthetic peptides induced cross-reactive antibodies in New Zealand White rabbits. Polyclonal antibodies raised to one of these peptides reacted with HIV-1 ENV gp120-related proteins, as determined by enzyme-linked immunosorbent assay and Western blotting techniques. These findings provide further evidence for a role of immunological cross-reactivity and molecular biomimicry in the development of peptide-based vaccines directed against viral or bacterial pathogens.

Animals↗
PubMed1998

Protein structure analysis using the resonant recognition model and wavelet transforms.

An approach based on the resonant recognition model and the discrete wavelet transform is introduced here for characterising proteins' biological function. The protein sequence is converted into a numerical series by assigning the electron-ion interaction potential to each amino acid from N-terminal to C-terminal. A set of peaks is found after performing a wavelet transform onto a numerical series representing a group of homologous proteins. These peaks are related to protein structural and functional properties and named characteristic vector of that protein group. Further more, the amino acids contributing mostly to a protein's biological functions, the so-called 'hot spots' amino acids, are predicted by the continuous wavelet transform. It is found that the hot spots are clustered around the protein's cleft structure. The wavelets approach provides a novel methods for amino acid sequence analysis as well as an expansion for the newly established macromolecular interaction model: the resonant recognition model.

Amino Acid Sequence↗
PubMed1998

Mapping acupuncture points using multi channel device.

The practice of acupuncture involves the stimulation of specific points on the skin called 'acupuncture points' which are small regions of local or referred pain that are more sensitive than surrounding tissue. The fact that acupuncture points can be identified subjectively as tender points and are found to have characteristic electrical properties suggest that they are functional entities rather than structural ones. These functional properties are used diagnostically in a clinical setting as pathology in a particular body location has been shown to correlate with increased tenderness and electrical conductivity of the 'corresponding' acupuncture point using electronic 'point locators', which measure the DC resistance of points compared to surrounding skin. Commercially available point locators generally utilize a metal locator probe and an indifferent electrode and are designed to produce an auditory output (usually a high pitched tone) when a point is located. These devices however, are open to criticism. They are unable to control for local variations in skin thickness, surface secretions, or pressure placed on the electrode, and are only able to measure a single point at a time. These make them time consuming to use and subjective to user bias in point selection. Furthermore these devices do not store data and are therefore unsuitable for producing a map of skin resistance, which can be accessed over time. To overcome some of the limitations of currently available single probe devices, we have designed a multi-channel probe capable of measuring and then mapping the skin resistance of multiple points.

Acupuncture Points↗
PubMed1997

The possibility of soliton/exciton transfer in proteins.

Recent reviews into the role of electron conduction within protein interactions have implicated the existence of soliton-like mechanisms that result in the conduction of electrons and bond vibrations along alpha-helix sections of proteins. This paper examines the possibility of solitons existing in other portions of a protein. It also investigates whether a soliton or exciton is implicated in vibrational signalling that may be used by biological systems to orchestrate bioprocesses as detailed by the Resonance Recognition Model.

Animals↗
PubMed1997

Acupuncture needles and the Seebeck effect: do temperature gradients produce electrostimulation?

Acupuncture may act through modifying bioelectric events and this may occur through different mechanisms including the application of external currents. According to the Seebeck effect which produces a potential difference when a temperature gradient is placed across a conductor, the physical properties of acupuncture needles may produce internal currents due to the temperature gradient across the needle when placed insitu. Such currents were detected when needles were differentially heated and these currents were found to be in the range capable of producing biological effects. The traditional design of acupuncture needles and traditional needle manipulations seem to maintain a temperature gradient across the needle and thus enhance the Seebeck effect.

Acupuncture Therapy↗
PubMed1995

Preliminary expansion of the resonant recognition model to incorporate multi variable analysis.

The Resonant Recognition Model (rrm) uses digital signal processing methods to investigate protein structure-function; and links the biological function of protein families to unique characteristic frequencies. The rrm originally used a single set of variables: the electron ion interaction potential (EIIP). Here the rrm has been expanded to include 242 sets of variables to analyse a sample of protein families. Despite the evident increase in complexity of the data, distinguishing patterns can be observed between the different protein families. The thus-obtained Signature Profiles (SP) indicate that proteins having similar overall functions may be identifiable and differentiated from others by their characteristic frequency signatures far more readily than with the single variable rrm spectra.

Amino Acid Sequence↗
PubMed1994

In vitro inhibition of the actions of basic FGF by a novel 16 amino acid peptide.

A composite procedure involving molecular modelling and a property-pattern algorithm, the Resonant Recognition Model (RRM), has been applied to structure-function studies with basic fibroblast growth factor (bFGF). Property-pattern characteristics for biological activity and receptor recognition for a group of FGF-related proteins were defined and then used to aid the design of a set of peptides which can act as bFGF antagonists. Molecular modelling techniques were then employed to identify the peptide within this set with the greatest conformational similarity to the putative receptor domain of bFGF. This 16 amino acid residue peptide (16mer), which exhibits no sequence homology to bFGF, antagonised the stimulatory effect of bFGF on fibroblast [3H]thymidine incorporation and cell proliferation, but exerted no effect itself in these in vitro bioassays.

Algorithms↗
PubMed1994

Macromolecular bioactivity: is it resonant interaction between macromolecules?--Theory and applications.

Biological processes in any living organism are based on selective interactions between particular biomolecules. In most cases, these interactions involve and are driven by proteins which are the main conductors of any living process within the organism. The physical nature of these interactions is still not well known. This paper represents a whole new view to biomolecular interactions, in particular protein-protein and protein-DNA interactions, based on the assumption that these interactions are electromagnetic in their nature. This new approach is incorporated in the Resonant Recognition Model (RRM), which was developed over the last 10 years. It has been shown initially that certain periodicities within the distribution of energies of delocalized electrons along a protein molecule are critical for protein biological function, i.e., interaction with its target. If protein conductivity was introduced, then a charge moving through protein backbone can produce electromagnetic irradiation or absorption with spectral characteristics corresponding to energy distribution along the protein. The RRM enables these spectral characteristics, which were found to be in the range of infrared and visible light, to be calculated. These theoretically calculated spectra were proved using experimentally obtained frequency characteristics of some light-induced biological processes. Furthermore, completely new peptides with desired spectral characteristics, and consequently corresponding biological activities, were designed.

Amino Acid Sequence↗
PubMed1992

Studies on protein-DNA interactions using the resonant recognition model. Application to repressors and transforming proteins.

The structural features of protein-DNA interactions have been evaluated using a new information theory algorithm for the analysis of protein structure/function dependence: the so-called resonant recognition model. The physicochemical basis of this analysis was firstly validated with the trp-repressor-operator interaction as a well-defined example. The amino acid and structural features predicted by these procedures to be crucial for repressor-operator interaction were found to be clustered around the known three-dimensional structure of the active site of the trp repressor. Similar methods of analysis have been extended to the less-well-defined example of the Ha-ras p21 protein family. The results of this analysis have indicated two distinct interactive regions in p21, one associated with the guanine-nucleotide-binding site, whilst the second is proposed to be associated with a binding site for an activator protein. These studies indicate that the p21 protein, besides the ability to function as a plasma-membrane-associated guanine-nucleotide-binding regulatory protein and bind free guanine nucleotides in the cytoplasm, has the structural ability to bind guanine incorporated in DNA. Thus, p21-related proteins may have the potential to function as an DNA-binding and regulating protein with the mode of upstream DNA binding closely related to their oncogenic function.

Animals↗
PubMed1991

Resonant recognition model and protein topography. Model studies with myoglobin, hemoglobin and lysozyme.

This study describes the further extension of the resonant recognition model for the analysis and prediction of protein--protein and protein--DNA structure/function dependencies. The model is based on the significant correlation between spectra of numerical presentations of the amino acid or nucleotide sequences of proteins and their coded biological activity. According to this physico-mathematical method, it is possible to define amino acids in the sequence which are predicted to be the most critical for protein function. Using sperm whale myoglobin, human hemoglobin and hen egg white lysozyme as model protein examples, sets of predicted amino acids, or so-called 'hot spots', have been identified within the tertiary structure. It was found for each protein that the predicted 'hot spots', which are distributed along the primary sequence, are spatially grouped in a dome-like arrangement over the active site. The identified amino acids did not correspond to the amino acid residues which are involved in the chemical reaction site of these proteins. It is thus proposed that the resonant recognition model helps to identify amino acid residues which are important for the creation of the molecular structure around the catalytic active site and also the associated physical field conditions required for biorecognition, docking of the specific substrate and full biological activity.

Animals↗
PubMed1989

Prediction of "hot spots" in interleukin-2 based on informational spectrum characteristics of growth-regulating factors. Comparison with experimental data.

The Resonant Recognition Model (RRM) is a theoretical method for analysis of protein and nucleotide sequences, based on the Fourier transform of the numerical representation of sequences. The amplitude spectrum of this transform is designated Informational Spectrum (IS). There are certain common frequencies in IS of growth-regulating factors. These characteristic frequencies may correlate with their roles in cell proliferation and metabolism, and in antitumor activity. IS of IL-2 has prominent characteristics in the main frequency domain of growth factors, frequency domain of antitumor factors, and frequency domain characteristic for IL-2-alpha receptor. By means of the inverse method for these 3 domains, the amino acids in the sequence of human IL-2 that may be relevant to its biological function, the so-called "hot spots", were predicted. The most probable hot spots, obtained in this way, are in the potential binding site of IL-2 to its receptor, which agrees with experimental data.

Amino Acid Sequence↗
PubMed1989

The relationship of the resonant recognition model to effects of low-intensity light on cell growth.

The resonant recognition model (RRM) is a model of protein-protein and protein-DNA interaction based on a significant correlation between spectra of numerical presentation of the amino acid or nucleotide sequences and their biological activity. Having compared absorption characteristics of photosensitive proteins with their RRM spectral characteristics we obtained a linear correlation between the RRM frequency space and real frequency space, which determines a scaling factor between these two frequency spaces. On applying the RRM model to several groups of peptide growth factors, characteristic RRM frequencies were revealed and the corresponding real characteristic frequencies for these groups of growth factors were calculated using the scaling factor previously obtained. The real frequency characteristics of growth factors obtained in this way correspond with maxima in the action spectra of low-intensity light irradiation effects on cell proliferation.

Animals↗
PubMedDate not supplied

'Hot spot' amino acid distribution in Ha-ras oncogene product p21: relationship to guanine binding site.

Although the rules which describe the atomic basis of structure-function relationships of proteins have yet to be deciphered, they are nevertheless coded within the framework of the amino acid and nucleotide sequence. The objectives of the present investigations were to document a composite, new approach for the evaluation of the structure-function dependencies of proteins based on the analysis of the informational content of the primary amino acid sequence as well as the topological and functional regions of a protein. This approach is validated with the example of the p21 Ha-ras oncogene family of proteins. Using this approach, amino acids crucial for p21 transforming activity have been identified and these amino acid residue assignments compared with experimental data.

Amino Acids↗