Biochemistry Software | Clinical Chemistry

Software that allows you to get preliminary results before conducting a laboratory experiment!

Biochemical Analysis Software

This section provides and describes in detail a numerical method for determining the effect of mutations on binding to small chemical molecules. The method we have developed makes it possible to numerically determine such a parameter as the stability of a complex molecular complex consisting of a protein and a small molecule. Changes in the resistance parameter for various oncogenic mutations in proteins upon binding to small chemicals molecules indicates the direction of the change in affinity and can serve as a good predictor, since it will allow the selection of small chemical molecules that increase the affinity for the selected oncogenic mutations in proteins.

Examples using small molecules are given below

Main purpose of the project
The purpose of this project is to develop a method that allows one to determine the effect of mutations from the known structure of a biological molecule on the binding affinity of a dimeric, tetrameric and other n-dimensional biological complex.

This method is suitable for small chemical molecules, as well as for transmembrane proteins, antibodies, antigens, immunoglobulins, cytosolic proteins.

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At the moment, it is necessary to conduct a biological experiment each time in order to determine how the effect of an oncogenic mutation on the affinity for a small molecule, it is necessary to experimentally investigate the cellular response and determine the concentration for the half-inhibition of the enzyme.

The goal of our project is to develop a method that allows one to determine the stability of a molecular complex using the local three-dimensional structures of interacting reagents, which in turn affects the affinity of the components, which is reflected in the cellular response.

What do we offer

Our team has developed an innovative method for determining the stability of chemical compounds, taking into account various oncogenic mutations
Why choose us?
Our software allows you to determine the direction of change in affinity, so you can significantly save on the following experimental methods:
Gel-shift assays
Aanalytical ultracentrifugation
Surface plasmon resonance
Spectroscopic assays
Affinity electrophoresis
Isothermal Calorimetry
The results of applying our technique can be of good help for the pre-experimental determination of such quantities as the affinity expressed by the dissociation constant or the half maximal inhibitory concentration (IC50).
Modeling the impact of point mutations on the stability of proteins. EXAMPLE 1 BIOLOGICAL SOFT
Thanks to the use of the software developed by us, you can determine the affinity of the biological complex before carry out the biological experiment. Binomial Soft will allow you to determine the range of variation of the experimental values in biological research. The purpose of our software development is to determine the affinity of a biological complex, which is comparable to such experimental values as Kd (a specific type of equilibrium constant), IC50 (the half maximal inhibitory 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.
Video instruction for using the software package
Our next example examines the effect of mutations in the heavy and light chains of Rituximab on binding to CD20. 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. The graph on the right presents the obtained numerical results on a logarithmic scale of the change in the value of lg (cond (W)). We have rotated the graph by 90 degrees for convenience of presentation, opposite each mutation the observed biological effect is shown, as well as the change in affinity in multiples.
Determination of antibody-antigen interaction using biological software
Technical information

Numerical determination of the stability
of the biocomplex taking into account
mutations in the protein

The document below provides a mathematical background. Thus, to express the conformational mobility of a polyatomic molecule in the IR region, one can use a formula of the form (43). At the same time, for correct use, it should be understood that the greater value (43) in comparison with the rest of the values will indicate that not large vibrations of individual chain links of a polyatomic molecule should be understood so that not the basic vibrations of an individual links protein complex can lead to a shift in the rest of the chain links of the polyatomic molecule and, as a consequence, to the exit from the state of equilibrium and transition to the state of the entire molecule.
Additional information on small chemical molecules
A number of structures in the Protein Data Bank (PDB) contain adenosine 5′-(β,γ-imido)triphosphate (AMPPNP), a nonhydrolysable analog of ATP in which the bridging O atom between the two terminal phosphate groups is substituted by the imido function. Under mild conditions imides do not have acidic properties and thus the imide nitrogen should be protonated. However, an analysis of protein structures containing AMPPNP reveals that the imide group is deprotonated in certain complexes if the negative charges of the phosphate moieties in AMPPNP are in part neutralized by coordinating divalent metals or a guanidinium group of an arginine.
[Deprotonated imidodiphosphate in AMPPNP-­containing protein structures ]
Tumor cell turnover modulates the speed of selection against drug resistance by amplifying the effects of competition and resistance costs
Adenylylimidodiphosphate: effect of contaminants on adenylate cyclase activity
ATP analogue adenylyl-imidodiphosphate (AMP-PNP)
Gefitinib is an anilinoquinazoline with antineoplastic activity. 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. Patients with advanced epidermal growth factor receptor (EGFR) mutated non–small- cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs), such as gefitinib, erlotinib, and afatinib, show improved progression-free survival (PFS) compared with standard chemo- therapy as first-line therapy.
Cancer researchers are medical scientists research on carcinoma (cancer)
Gefitinib (Iressa®) is a selective small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR TKI) indicated for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating mutations of EGFR tyrosine kinase.
Gefitinib (Iressa) is an orally active TK inhibitor
(TKI) that blocks signal transduction pathways implicated
in cancers. The structures of the L858R and G719S mutants complexed with either AMPPNP or the inhibitors, gefitinib and AEE788, revealed that the overall conformation and ligand-binding modes are very similar to those of the wild-type EGFR-TK in the active
cancer treatment research medicine software
CH7233163 as having the potential to overcome EGFR-Del19/T790M/C797S. CH7233163 showed potent antitumor activities against tumor with EGFR-Del19/T790M/C797S in vitro and in vivo. In addition to EGFR-Del19/T790M/C797S, the characterization assays showed that CH7233163 more selectively inhibits various types of EGFR mutants (e.g., L858R/T790M/C797S, L858R/T790M, Del19/T790M, Del19, and L858R) over wild type.
cancer, oncology, medicine, research, software
Rociletinib (CO-1686) is an irreversible, mutant-selective EGFR inhibitor[52]. 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 [53]
Cancer. Medicine. software oncology research
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