Prediction of intrinsically disordered regions in proteins using signal processing methods: application to heat-shock proteins.

Heat-shock protein (HSP)-based immunotherapy is believed to be a promising area of development for cancer treatment as such therapy is characterized by a unique approach to every tumour. It was shown that by inhibition of HSPs it is possible to induce apoptotic cell death in cancer cells. Interestingly, there are a great number of disordered regions in proteins associated with cancer, cardiovascular and neurodegenerative diseases, signalling, and diabetes. HSPs and some specific enzymes were shown to have these disordered regions in their primary structures. The experimental studies of HSPs confirmed that their intrinsically disordered (ID) regions are of functional importance. These ID regions play crucial roles in regulating the specificity of interactions between dimer complexes and their interacting partners. Because HSPs are overexpressed in cancer, predicting the locations of ID regions and binding sites in these proteins will be important for developing novel cancer therapeutics. In our previous studies, signal processing methods have been successfully used for protein structure-function analysis (i.e. for determining functionally important amino acids and the locations of protein active sites). In this paper, we present and discuss a novel approach for predicting the locations of ID regions in the selected cancer-related HSPs.

Low intensity microwave radiation as modulator of the L-lactate dehydrogenase activity.

In this study, we investigated experimentally the possibility of modulating protein activity by low intensity microwaves by measuring alternations of L: -Lactate Dehydrogenase enzyme (LDH) activity. The LDH enzyme solutions were irradiated by microwaves of the selected frequencies and powers using the Transverse Electro-Magnetic (TEM) cell. The kinetics of the irradiated LDH was measured by continuous monitoring of nicotine adenine dinucleotide, reduced (NADH) absorbance at 340 nm. A comparative analysis of changes in the activity of the irradiated LDH enzyme versus the non-radiated enzyme was performed for the selected frequencies and powers. It was found that LDH activity can be selectively increased only by irradiation at the particular frequencies of 500 MHz [electric field: 0.02 V/m (1.2 × 10⁻6 W/m²)-2.1 V/m (1.2 × 10⁻² W/m²)] and 900 MHz [electric field: 0.021-0.21 V/m (1.2 × 10⁻4 W/m²)]. Based on results obtained it was concluded that LDH enzyme activity can be modulated by specific frequencies of low power microwave radiation. This finding can serve to support the hypothesis that low intensity microwaves can induce non-thermal effects in bio-molecules.

Review of studies on modulating enzyme activity by low intensity electromagnetic radiation.

This paper is a compilation of our findings on non-thermal effects of electromagnetic radiation (EMR) at the molecular level. The outcomes of our studies revealed that that enzymes' activity can be modulated by external electromagnetic fields (EMFs) of selected frequencies. Here, we discuss the possibility of modulating protein activity using visible and infrared light based on the concepts of protein activation outlined in the resonant recognition model (RRM), and by low intensity microwaves. The theoretical basis behind the RRM model expounds a potential interaction mechanism between electromagnetic radiation and proteins as well as protein-protein interactions. Possibility of modulating protein activity by external EMR is experimentally validated by irradiation of the L-lactate Dehydrogenase enzyme.

An XML based middleware for ECG format conversion.

With the rapid development of information and communication technologies, various e-health solutions have been proposed. The digitized medical images as well as the mono-dimension medical signals are two major forms of medical information that are stored and manipulated within an electronic medical environment. Though a variety of industrial and international standards such as DICOM and HL7 have been proposed, many proprietary formats are still pervasively used by many Hospital Information System (HIS) and Picture Archiving and Communication System (PACS) vendors. Those proprietary formats are the big hurdle to form a nationwide or even worldwide e-health network. Thus there is an imperative need to solve the medical data integration problem. Moreover, many small clinics, many hospitals in developing countries and some regional hospitals in developed countries, which have limited budget, have been shunned from embracing the latest medical information technologies due to their high costs. In this paper, we propose an XML based middleware which acts as a translation engine to seamlessly integrate clinical ECG data from a variety of proprietary data formats. Furthermore, this ECG translation engine is designed in a way that it can be integrated into an existing PACS to provide a low cost medical information integration and storage solution.

A new approach to revealing functional residues from analysis of protein primary structure.

A protein's biological function is encrypted within its primary structure. Nevertheless, revealing protein function from analysis of its primary structure is still unsolved problem. In this article we present a new methodology for determining functionally significant amino acid residues in proteins sequences, which is based on time-frequency signal analysis and Smoothed Pseudo Wigner Ville distribution (SPWV). This investigation is the extension of the Resonant Recognition Model (RRM) approach designed for structure-function analysis of proteins and DNA. The RRM is based on the finding that there is a significant correlation between spectra of the numerical presentation of amino acids and their biological activity. The RRM assumes that the selectivity of protein interactions is based on the resonant electromagnetic energy transfer at the specific frequency for each interaction. In this study Cytochrome C, Glucagon, and Hemoglobin proteins were used as the protein examples. By incorporating the SPWV distribution in the RRM, we can define the active regions along the protein molecule. In addition, it was also shown that our computational predictions are corresponding closely with the experimentally identified locations of the active/binding sites for the selected protein examples.

The effect of electromagnetic radiation (550-850 nm) on 1-lactate dehydrogenase kinetics.

PURPOSE: This work is based on our earlier research of the Resonant Recognition Model (RRM), where we have proposed that protein activation is electromagnetic in its nature. In this study we investigated experimentally the possibility of modulating the protein activity by the electromagnetic radiation of the specific frequency. The concept is studied here by applying a visible light radiation to example of 1-Lactate Dehydrogenase enzyme (LDH). MATERIALS AND METHODS: The selected LDH example is radiated by monochromatic visible light in a frequency range predicted computationally by the RRM. The kinetics of the irradiated LDH is measured by continuous monitoring of the NADH absorption at 340 nm. RESULTS: A comparative analysis of the LDH enzyme activity before and after the electromagnetic field (EMF) exposures is performed. It was found that the LDH activity is selectively increased only by the radiation at the particular wavelengths of 595 nm and 828 nm. These experimentally determined wavelengths of the applied EMF are within the range predicted by the RRM. CONCLUSIONS: Results reveal the LDH activity was modulated by the EMF exposures at the computationally predicted frequencies. The RRM concept presented provides new insights into proteins susceptibility to perturbation by electromagnetic radiation and possibility to program, predict, design and modify proteins and their bioactivity.

Investigation of the mechanisms of electromagnetic field interaction with proteins.

In our earlier work we have proposed that protein activation is electromagnetic in its nature. This prediction is based on the Resonant Recognition Model (RRM) where proteins are analyzed using digital signal processing (DSP) methods applied to the distribution of free electron energies along the protein sequence. This postulate is investigated here by applying the electromagnetic radiation to example of L-Lactate Dehydrogenase protein and its biological activity is measured before and after the exposures. The concepts presented would lead to the new insights into proteins susceptibility to perturbation by exposure to electromagnetic fields and possibility to program, predict, design and modify proteins and their bioactivity.