In this section you can read, familiarize and free download the research publications of our group
Analysis of electrostatic interaction dimeric complexes. Part I. Selection method inhibitors to derivatives APP
[On Jule 2020]
The article presents an original method that allows to obtain high-quality assessment of the ability of amyloid peptides to form high molecular weight structures, to solve the stability problem of amyloid dimeric complexes using the given values: the logarithm of the condition number of the potential matrixenergies of paired electrostatic interactions between amino acid residuals and differential entropy for the case of multidimensional normal distribution, which allowed to determine the formation of structures of a higher order: oligomers, protofibrils, fibrils as they reach the state of stability. Thus, the main direction in blocking the formation of amyloids during their formation of high molecular weight structures is to ensure achievement by amyloids of a stable state at the level of dimeric complexes.
keywords: Alzheimer’s disease, amyloids, key amino acid residues, differential entropy, condition number.
Analysis of electrostatic interaction dimeric complexes.Part II. Criteria and conditions for derivative inhibitors APP protein.
The article presents the calculations, selection methods and gives the characteristics of inhibitorytori of formation of high molecular structures by amyloid peptides, given explanation of their blocking action. In the presented article, we consider in detail biophysical requirements for inhibitors, criteria and conditions for their selection, which some will block the formation of high-order structures by amyloids. Modified peptides were studied as inhibitors, which will form stable dimers with amyloid peptides, thereby preventing the introduction of amyloids into all new biochemical reactions. The article discusses the entry of amyloids into biochemical reactions with similar amyloid peptides and their possible reaction with the walls of blood vessels will not be considered. Moreover, the following criteria were used as a criterion for assessing the stability of the dimeric complex: the logarithm of the condition number of the matrix of potential energy of pairwise electrostatic interaction between amino acid residues and differential entropy for the case of a multidimensional normal distribution.
keywords: Alzheimer’s disease, amyloids, key amino acid residues, peptides, condition number, change in differential entropy measure.
Point mutations and stability protein dimers Bcl-2 protein family
INTRODUCTION The present study is devoted to the development of a biophysical approach for the selection of highly selective peptides to target proteins that inhibit/activate their biological activity in various types of pathological diseases. The method developed in this study enables assessing the change in the stability of protein complexes upon replacement of amino acid residues, as was demonstrated by the example of protein dimers Bcl2– BH3-Bax.
Keywords: dissociation constant, three-dimensional structure, entropy, amino acid residue
Analysis of electrostatic interactions of amino acid of residues on the example of the formation of the dimer Nap1 − Nap1
[On March 2020]
A new method, which analyzes the potential energy of electrostatic interaction of protein complexes at point replacements of amino acid residues assuming a three-dimensional structure of the complex on the example of formation of a Nap1–Nap1 dimer, has been presented. Maps of potential energy of electrostatic interaction of paired amino acid residues of participating proteins have been developed.
INTRODUCTION In this study, a new method is presented, on the basis of which drug inhibitors for target proteins in analogy with previously developed monoclonal antibodies such as trastuzumab and cetuximab, can be developed. In this case, trastuzumab binds the HER2 receptor and slows down cell division ; in turn, cetuximab is an epidermal growth factor receptor (EGFR) inhibitor  and is employed for metastatic colorectal cancer therapy and metastatic non-small cell lung cancer. The developed method allows one to modify existing known drugs for cancer pathology therapy in order to increase their affinity to target receptors and consider the effect of point mutations in proteins, which can be observed in various types of tumors as exemplified by somatic mutation of the BRAF gene in the case of melanoma .
Keywords: conformation, hydrophobic interactions, key amino acid residues, cluster
Mathematical Modeling of Protein Complexes
© Springer Nature Switzerland AG 2018
Applies computational methods to simulate the electrostatic interaction of protein molecules to form complexes and domains
Predicts amino acid sequences with specific physical properties
Helps to improve the efficiency of experiments
Biological and Medical Physics, Biomedical Engineering The authors dedicate this book to the memory of Prof. Narbut M. A. The monograph is addressed to researchers and specialists in biomedical physics, molecular biology interested in the development and application of mathematical methods in medical research. This book is devoted to the physical and mathematical modeling of the formation of complexes of protein molecules. The models developed show remarkable sensitivity to the amino acid sequences of proteins, which facilitates experimental studies and allows one to reduce the associated costs by reducing the number of measurements required according to the developed criteria. These models make it possible to reach a conclusion about the interactions between different amino acid chains and to identify more stable sites on proteins. The models also take the phosphorylation of amino acid residues into account. At the end of the book, the authors present possible directions of application of their physical and mathematical models in clinical medicine.
Laser Interaction with Biological Material
One of the most important areas of application of laser radiation is biomedical optics. Here, laser sources are used for diagnosis, therapy, or surgery. Note that for the development of new methods of laser biomedical diagnostics, a detailed study of the propagation of light in biological tissues is required, as theoretical studies improve understanding of the optical measurements, increase capacity, reliability, and usefulness of optical technologies. To solve these problems in the first place the most informative indicators of the functioning of the organism must be chosen. These indicators are the results of the analysis of peripheral blood. Peripheral blood provides the complete information on the status of the human organism. A comprehensive study of the characteristics of light scattering and absorption can quickly detect intact physiological and morphological changes in the cells due to thermal, chemical, antibiotic treatments, etc.
Mathematical Modeling of Linear Docking. I. Determination of Regions of Binding of Protein Molecules
We report on the results of mathematical simulation of the interaction of various sequences of proteins Mdm2, P53, and Nap1 in accordance with the developed algorithms that were used for identifying the region of binding of various proteins during the formation of biological complexes P53–Mdm2, Mdm2–Mdm2, and Nap1–Nap1. The approach developed in this work will make it possible to determine active regions of binding of polypeptide chains of various proteins and to choose and synthesize highly selective peptides that will be bound in the active center of a protein and will lead to its activation or inhibition and blocking of its biological functions.
Mathematical Modeling of Linear Docking. II. Estimating the Effect of Point Mutations on the Affinity between Protein Molecules
A new method enabling the qualitative determination of the dissociation constant of peptides to full-length proteins and the estimation of the effect of point mutations in peptides on the stability of a formed complex with whole proteins was presented. Based on the developed approach, a qualitative correlation was revealed between the obtained results and the dissociation constant using the formation of a biocomplex of the Bmf, Puma, Bad, Hrk, Bax, Bik, Noxa, Bid, Bim, and Bak BH3-peptides and the Bcl-xl protein and a biocomplex of the Bax BH3-peptides and the Bcl-2 protein with consideration for the replacement of amino acid residues as an example.
Mathematical modeling of the temperature effect on the character of linking between monomeric proteins in aqueous solutions
This work is devoted to the mathematical modeling of the temperature effect on the stability of H2A–H2B and Н3–H4 histone dimers by studying their behavior in different temperature regimes of 20–50°C. The study of the thermal stability of these two dimers in aqueous solutions at different temperatures has revealed their multifarious behavior at temperatures at 20–50°C. Analysis has shown that dimer Н3–H4 is prone to aggregation due to an increase in the force of linking between histones Н3 and H4. Studies of the behavior of histone dimer H2A–H2B have disclosed different temperature transitions in its structure with a maximum peak at a temperature 45°C.
Mathematical modeling the formation of a histone octamer
A physical model of the interaction of protein molecules and their ability to form complex biological systems for the in vitro case in a solution of monovalent salt has been developed. Their reactive abilities using the methods of electrostatics based on the example of the step-by-step formation of the histone octamer from the H2A, H2B, H3, and H4 proteins have been studied. To analyze the ability of protein molecules to form compounds the matrix of potential energy of interactions between protein molecules in solutions with different concentrations of monovalent salt has been examined.
Mathematical simulation of complex formation of protein molecules allowing for their domain structure
A physical model of the interactions between protein molecules has been presented and an analysis of their propensity to form complex biological complexes has been performed. The reactivities of proteins have been studied using electrostatics methods based on the example of the histone chaperone Nap1 and histones H2A and H2B. The capability of proteins to form stable biological complexes that allow for different segments of amino acid sequences has been analyzed. The ability of protein molecules to form compounds has been considered by calculating matrices of electrostatic potential energy of amino acid residues constituting the polypeptide chain. The method of block matrices has been used in the analysis of the ability of protein molecules to form complex biological compounds.
Mathematical simulation of interactions of protein molecules and prediction of their reactivity
A physical model of interactions of protein molecules has been developed. The regularities of their reactivity have been studied using electrostatics methods for two histone dimers H2A–H2B and H3–H4 assembled from monomers. The formation of histone dimers from different monomers has been simulated and their ability to the formation of stable compounds has been investigated by analyzing the potential energy matrix using the condition number. The results of a simulation of the electrostatic interaction in the formation of dimers from complete amino acid sequences of selected proteins and their truncated analogs have been considered. The calculations have been performed taking into account the screening of the electrostatic charge of charged amino acids for different concentrations of the monovalent salt using the Gouy–Chapman theory.
Measurement of sizes of colloid particles using dynamic light scattering
Size distribution functions of colloid particles are obtained with the aid of dynamic light scattering for both polarized and depolarized components. Electron microscopy of the colloid particles is used to construct size distribution histograms. Numerical analysis yields good agreement of the experimental and theoretical size distributions. The size distribution function is derived from the solution to the corresponding integral equations using the Tikhonov regularization procedure.
Simulation of the type of coralin alkaloid-DNA binding
Interaction between a synthesized coralin protoberberine alkaloid and the DNA double helix of the calf’s thymus in a salt solution is studied by optical absorption spectroscopy and spectropolarimetry. The dependence of the spectral characteristics of the alkaloid on a ratio between the DNA base pair concentration and the alkaloid molecule concentration is considered. The parameters of bonds between the coralin alkaloid and the DNA double helix are determined using modified McGhee-von Hippel equations.