Toolbox medical innovations

Biological software
For reducing the cost of conducting biochemical experiments
In connection with the many meetings and negotiations held with startups, business angels, managers, investors, development managers, researchers, it was decided to simplify the presentation of material from quantum mechanical justification to clear visual presentations with colorful design. For a more detailed acquaintance with the presented method, you can familiarize yourself in the section Publications. Part of the program code with examples is given and detailed in the monograph
Mathematical Modeling of Protein Complexes.
The purpose of a visual presentation is to facilitate understanding.

It is also always worth remembering that the key to successful work
this is a well-coordinated teamwork to obtain a quality result.

Tatiana Koshlan

Why are we investigating electrostatic interactions?

- we are often asked about this, because "there are many other interactions."

This part is devoted to a frequently asked question regarding electrostatic interactions, which are the main ones in our research.

Solvation (from lat. Solvo "dissolve") - electrostatic interaction between particles (ions, molecules) of a dissolved substance and a solvent. Solvation in aqueous solutions is called hydration. The molecular aggregates formed as a result of solvation are called solvates (in the case of water, hydrates)

Van der Waals forces (Van der Waals forces) are the forces of intermolecular (and interatomic) interaction with an energy of 10–20 kJ / mol. This term originally denoted all such forces, in modern science it is usually applied to the forces arising from the polarization of molecules and the formation of dipoles.

Classification of van der Waals forces:
The van der Waals interaction consists of three types of weak electromagnetic interactions:

Orientation forces, dipole-dipole attraction. It is carried out between molecules that are permanent dipoles. An example is HCl in liquid and solid state. The energy of this interaction is inversely proportional to the cube of the distance between the dipoles.

Dispersive attraction (London forces, dispersion forces). They are due to the interaction between the instantaneous and the induced dipole. The energy of this interaction is inversely proportional to the sixth power of the distance between the dipoles.

Induction attraction (polarization attraction). Interaction between permanent dipole and induced (induced). The energy of this interaction is inversely proportional to the sixth power of the distance between the dipoles.

The dipole moment is an important molecular constant that characterizes the electrical symmetry of a molecule. Knowledge of the magnitude of the dipole moment is necessary for studying the nature of chemical bonds, assessing the strength of donor-acceptor and intermolecular bonds, for quantum-chemical calculations.

Electric dipole moment is a vector physical quantity that characterizes, along with the total charge (and rarely used higher multipole moments), the electrical properties of a system of charged particles (charge distribution) in the sense of the field they create and the action of external fields on it. After the total charge and the position of the system as a whole (its radius vector), the main characteristic of the configuration of the charges of the system when observing it was published

Dispersion forces (dispersive attraction, London forces, London dispersion forces, LDF) are the forces of electrostatic attraction of instantaneous and induced (induced) dipoles of electrically neutral atoms or molecules.

A hydrogen bond is a form of association between an electronegative atom and a hydrogen atom H, covalently bonded to another electronegative atom. N, O, or F can act as electronegative atoms. Hydrogen bonds can be intermolecular or intramolecular

Donor-acceptor interaction - charge transfer between donor and acceptor molecules without the formation of a chemical bond between them (exchange mechanism); or the transfer of a lone electron pair from a donor to an acceptor, leading to the formation of a bond (donor-acceptor mechanism).

EXAMPLE. Algorithm for determining the direction of change in affinity Antibody-Antigen [CD20-Retuximab]

Our method will include modification of flexible chains of immunoglobults, stepwise testing of each antibody to antigen, determination of key amino acid residues, range of changes in affinity.

Startup pitch deck.

Startup pitch decks of high lifescience innovations.
The main goal
The main goal of our software is to reduce the cost of biochemical experiments by obtaining preliminary information on the interaction of chemical compounds.

Software tools for structure analysis of biochemical experiments:

      Inhibitory potency and binding ability of small molecule
                  Inhibitor dissociation constants for the WT and mutant kinases
                              Enzyme kinetic parameters
                                          Explain the enhanced drug sensitivity of different mutants
                                                      Inhibitor dissociation constants for the WT and mutant kinases
                                                                  Changing in the binding site caused by
                                                                  the mutation on the enzyme's binding affinity for TKIs

                                                                              Enzyme kinetic assays and IC50 determinations
                                                                                          Inhibitor binding constants
                                                                                                      The drug resistance
                                                                                                              UP TITLE
                                                                                                              Thanks to the use of the software developed by us, you can determine the affinity range of the biological complex before carry out the biological experiment.

                                                                                                              Binomial Soft will allow you to determine the affinity range in biological research.

                                                                                                              The purpose of our software development is to determine the affinity range of a biological complex, which is comparable to such experimental values as Kd (a specific type of equilibrium constant), EC50 (half maximal effective concentration), ΔH, potential energy of interaction.

                                                                                                              Moreover, we want to share our method with other people how to use methods by other laboratories around the world, as this will significantly accelerate the development of
                                                                                                              drugs against other diseases. Take the development of targeted drugs to a
                                                                                                              new level in the field of exact

                                                                                                              Why choose us?
                                                                                                              Our software allows you to determine the direction of affinity change, so you can significantly save on the following experimental methods:
                                                                                                              Gel-shift assays
                                                                                                              Aanalytical ultracentrifugation
                                                                                                              Surface plasmon resonance
                                                                                                              Spectroscopic assays
                                                                                                              Affinity electrophoresis
                                                                                                              Isothermal Calorimetry
                                                                                                              Introductory video on the practical use of our software
                                                                                                              Using our software package you can determine the range of changes in affinity and then select only those modifications for further experimental research that meet the set objectives, for example, antibody modifications that will increase the affinity to the antigen, but will not lead to aggregation of antibodies among themselves.
                                                                                                              Description of the software package for determining the stability of protein molecules.
                                                                                                              free video editing software,toolbox medical innovations
                                                                                                              TUTORIAL BIOLOGICAL SOFT. The figures show two graphs showing the results of the effect of mutations in the BAK peptide on binding to the Bcl-xl protein. The graph on the left is from an experimental study.
                                                                                                              The figure shows a tetramer consisting of two CD20 transmembrane proteins and two FABs, heavy and light chains We will introduce five mutations in turn into the active binding site with CD20 and analyze the change in stability.

                                                                                                              Below are some biological research areas to which our software package can be applied.

                                                                                                              The purpose of this project is to develop a method (biological software)that allows one to determine the effect of mutations from the known structure of a biological molecule on the binding affinity

                                                                                                              Molecular Therapies of Cancer

                                                                                                              Our team has developed an innovative method for determining the stability of chemical compounds, taking into account various oncogenic mutations. Useful application of the obtained numerical results
                                                                                                              Gefitinib inhibits the catalytic activity of numerous tyrosine kinases including the epidermal growth factor receptor (EGFR), which may result in inhibition of tyrosine kinase-dependent tumor growth. Specifically, this agent competes with the binding of ATP to the tyrosine kinase domain of EGFR, thereby inhibiting receptor autophosphorylation and resulting in inhibition of signal transduction.
                                                                                                              The T790M mutation of EGFR increases the ATP affinity of the G719S mutant, explaining the acquired drug resistance of the double mutant. Structural analyses of the G719S/T790M double mutant, as well as the wild type and the G719S and L858R mutants, revealed that the T790M mutation stabilizes the hydrophobic spine of the active EGFR-TK conformation.
                                                                                                              Rociletinib (CO-1686) is an irreversible, mutant-selective EGFR inhibitor. It is a medication developed to treat non-small cell lung carcinomas with a specific mutation. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor. It was being developed by Clovis Oncology as a potential treatment for non-small-cell lung cancer
                                                                                                              Imatinib is specific tyrosine kinase receptor inhibitor that is used in the therapy of Philadelphia chromosome-positive chronic myelogenous leukemia and gastrointestinal stromal tumors, both of which are marked by an abnormal, constitutively expressed tyrosine kinase that causes unregulated cell growth.

                                                                                                              Our research can be divided into fundamental (basic) and applied biological researches.

                                                                                                              Molecular biophysics is the study of the physical principles governing biomolecular systems. It seeks to explain biological function in terms of molecular structure, dynamics and organization, from single molecules to supramolecular structures.
                                                                                                              Now let's analyze, and then perform example of replacing an amino acid residue in a Bak peptide when it interacts with the whole protein Bcl xl, which leads to an increase in the affinity of the peptide to the protein. Let us consider in more detail the three-dimensional structure of this dimer. Initially, we have a 3D structure of a dimer, in which the Q77L substitution in the Bak peptide is performed. The overall structure of BAKQ77L was not significantly affected by the mutation, and the side chain of L77 is oriented identically to the wild-type glutamine at this position on the solvent-exposed surface of the (BH3) helix.
                                                                                                              Example 2: guide to biological software
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                                                                                                              Antibody Affinity

                                                                                                              Biophysics of the affinity of the antibody-antigen biocomplex
                                                                                                              Our group developed an innovative method in biology for antibody-antigen development. You don't have to spend money to carry out the experiment.
                                                                                                              The correct determination of antibody affinity is crucial for antibody development as a wrong setup of the experiments may result in the further development of the wrong candidate antibody. This can result in low in vivo efficacy, especially when high-affinity antibodies are needed, for example, for neutralizing antibodies.
                                                                                                              Our group has developed an innovative research technique for such a complex using Data Science
                                                                                                              Learn More
                                                                                                              Coronavirus (Covid-19) is a world pandemic. A step-by-step guide to the analysis of affinity of interaction by Soft using
                                                                                                              This article describe a detailed method for selecting inhibitors based on modified natural peptides for the SARS-CoV protein spike glycoprotein. The selection of inhibitors is carried out by increasing the affinity of the peptide to the active center of the protein. The article also provides a step-by-step guide to the analysis of affinity of interaction by comparing 3 criteria, presents an analysis of energy interactions between the active center of a protein and the wild-type peptide interacting with it and taking into account modifications of the latter.
                                                                                                              Learn More
                                                                                                              New Approaches for Aggregation Mechanisms in Amyloids
                                                                                                              We concluded that the dimers of mutant amyloids form stable and unstable dimeric complexes. If the dimeric complex is stable, then the formation of high molecular weight structures was much slower. This was due to the fact that the stable amyloid peptides were in no hurry to enter into chemical reactions with other amyloid peptides to achieve equilibrium.
                                                                                                              It remained to solve the question: how will we determine the stability of the dimeric complex
                                                                                                              Learn More
                                                                                                              DATABASE OF TARGETED ANTITUMOR THERAPY FOR EGFR PROTEINS: HER2 AND HER3. Soft application.
                                                                                                              Our method is molecularly selective, targeting certain oncogenic molecules, namely the EGFR family of tyrosine kinases, which occupy a significant share in the causes of oncogenic diseases. The diagram shows the percentage of mutations in proteins of the EGFR family in non-small cell lung cancer. Most people have relatives or friends who are sick or who have already left us. In 2017, 9.6 million people are estimated to have died from the various forms of cancer. Every sixth death in the world is due to cancer, making it the second leading cause of death — second only to cardiovascular diseases.
                                                                                                              What is hydrophobic interaction?
                                                                                                              The most common explanation is that hydrophobic molecules "do not like" to interact with the aqueous environment. We obtained the values of hydrophobic interactions, calculated their value, developed a method for determining the range of interactions, and developed a graphical representation using soft, math, data science. You can free download soft and learn Data Scince
                                                                                                              hydrophobic interactions
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                                                                                                              What researches are you interested in?
                                                                                                              Here you can ask a question, talk about the goals of your research.
                                                                                                              You can leave a comment by choosing several options or send your message
                                                                                                              Or you can choose the most suits for you
                                                                                                              Choose the right option
                                                                                                              Additional information
                                                                                                              Protein-protein interactions. Miscellaneous.
                                                                                                              Examples of various calculations taking into account three-dimensional structure, as well as without taking into account three-dimensional structure
                                                                                                              metastatic breast cancer, breast cancer, colon cancer, what is colon cancer


                                                                                                              3D Maps
                                                                                                              p73 is a structural and functional homologue of the p53 tumor suppressor protein. Like p53, p73 induces apoptosis and cell cycle arrest and transactivates p53-responsive genes, conferring its tumor suppressive activity. In addition, p73 has unique roles in neuronal development and differentiation.
                                                                                                              metastatic breast cancer, breast cancer, colon cancer, what is colon cancer

                                                                                                              P53-P53, P63-P63, P73-P73 protein interactions

                                                                                                              Linear Docking. Bellow we present the results of mathematical simulation of the interaction of various sequences of proteins p53, p63, and p73 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-p53, p63-p63, and p73-p73.
                                                                                                              metastatic breast cancer, breast cancer, colon cancer, what is colon cancer

                                                                                                              Nap1-Nap1 interactions (3D Map)

                                                                                                              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.
                                                                                                              predictive oncology, radiation oncology, hematology oncology, breast cancer metastasis, lung cancer metastasis, colon cancer

                                                                                                              Nap1-Nap1, Mdm2-Mdm2

                                                                                                              Linear Docking. Bellow we present two algorithms are developed: Algorithm 1 and Algorithm 2. Algorithm 1 was developed in order to search for the interaction of a polypeptide chain of a full-length protein with short active region.

                                                                                                              Behind the big data

                                                                                                              Fundamental (basic) research

                                                                                                              Mathematical [math] methods, soft, data science and their physical application

                                                                                                              Advance techniques and Physical Applications provides a wide range of basic math concepts and methods, which are relevant to biophysic theory and biomolecule. This page is devoted to the physical and mathematical modeling of the formation of complexes of protein molecules, antibody and amyloid peptide (alzheimer desease). Real techniques show remarkable sensitivity to the amino acid sequences of proteins, which facilitates experimental studies in lab and allows one to reduce the associated costs by reducing the number of measurements required according to the developed criteria in experimental lab. 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 via control techniques, soft and Data Science. The models also take the phosphorylation of amino acid residues into account.
                                                                                                              You can download soft for antibody cost saving and learn Data Scince
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                                                                                                              Interaction of hydrophobic molecules

                                                                                                              It became possible to quantify the hydrophobic effect using data science, soft and biophisical methods: calculate the magnitude and value of the potential energy of pairwise electrostatic interactions between each pair of hydrophobic amino acid residues of two protein.
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                                                                                                              CALCULATION OF ENTROPY CHANGE

                                                                                                              For obtain a numerical estimate of this interaction we estimate the change differential entropy for one-dimensional and multidimensional case using software, data scince and math.
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                                                                                                              Kogbetliantz's algorithm

                                                                                                              Kogbetliantz's algorithm for the singular-value decomposition (SVD) of an arbitrary matrix can be viewed as a natural extension of Jacobi's method for the eigenvalue decomposition of a symmetric, Hermitian, or normal matrix.
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                                                                                                              Singular Value Decomposition

                                                                                                              In linear algebra, the Singular Value
                                                                                                              Decomposition (SVD) of a matrix is a factorization of that matrix
                                                                                                              into three matrices.You can use this technique and also learning data science
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                                                                                                              Debye length

                                                                                                              The Debye length (also called Debye radius), named after Peter Debye, is a measure of a charge carrier's net electrostatic effect in a solution and how far its electrostatic effect persists.
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                                                                                                              The Gouy–Chapman theory

                                                                                                              The Gouy-Chapman theory describes a rigid charged surface, with a cloud of oppositely charged ions in the solution, the concentration of the oppositely charged ions decreasing with distance from the surface. This is the so-called diffuse double layer.
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                                                                                                              Algorithm rotation

                                                                                                              This algorithm, taking into account the rotation of one amino acid
                                                                                                              residue allows you to find the stability of protein-protein complexes, peptide-peptide complex, peptide-protein complex with a
                                                                                                              known amino acid sequence and with the known three-dimensional structure from X-ray analysis.
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                                                                                                              Static algorithm

                                                                                                              An algorithm and software package was developed for analyzing protein interactions, taking into account their three-dimensional
                                                                                                              structure from the PDB database.
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                                                                                                              Mathematical modelling of the effect of phosphorylation of biological complexes

                                                                                                              A physical and mathematical model was developed to take into account the phosphorylation effect
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