Deep learning in cancer pathology

AI Biomarker Discovery

Calculation of thermodynamic equilibrium shift for each patient in personalized medicine.

Familiarize yourself with the main list of calculations.

Step-by-step approaches in checking the correctness of building X-ray structures (PDB files)

Biomarker development concept

Organometallic inhibitor CNS292

Biochemical scheme with interaction of wild-type BRAF proteins

Organometallic inhibitor CNS292

3Q4C

A cocrystal structure of CS292 in complex with the BRAF kinase domain reveals that CS292 binds to the ATP binding pocket of the kinase and is an ATP competitive inhibitor. The structure of the kinase–inhibitor complex also demonstrates that CS292
binds to BRAF in an active conformation and suggests a mechanism for regulation of BRAF by phosphorylation and BRAFV600E oncogene-induced activation. The structure of CS292 bound to the active form of the BRAF kinase also provides a novel scaffold for the design of BRAFV600E oncogene
selective BRAF inhibitors for therapeutic application.

[(BRAF-BRAF)]+S.C.M.____________________[(BRAF-S.C.M.)(BRAF)]

[(BRAF-S.C.M.)]+[BRAF]__________________[(BRAF-S.C.M.)(BRAF)]

CS292 Concentrarion ( M x 10____ )

-6

The most potent BRAF inhibitor, CS292, was also shown to have an 2-fold selectivity for BRAFV600E (IC50 = 0.21 мM) over the wild-type enzyme

Agreement between calculated and experimental data

Dose–response curves of CS292 from an ELISA-based BRAF kinase inhibition assay

BRAF

BRAF

PDB:3Q4C

Fig. Crystal Structure of Wild Type BRAF kinase domain in complex with organometallic inhibitor CNS292

Fig. Graph for determining the normality of the distribution for the subsequent determination of the change in information entropy.

number condition
4.95007946258379
4.94881380912470

max eigenvalue
4.665616e-19
4.651594e-19

min eigenvalue
5.233950e-24
5.233449e-24

error computational SVD
1.6386e-19
1.6523129e-19

3q4c (wt)
3q4c(V600E)

Figure 3: Dependence of RMSD(root-mean-square deviation) on the configuration number

The fig.1 shows a rapidly oscillating character, which indicates the impossibility of finding a local minimum: optimization completed because at the initial point, the objective function is nondecreasing in feasible directions. As follows from the fig.1 the local minimum no found.

Dependence of RMSD(root-mean-square deviation) on the configuration number.