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6PLenary session 17
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of Computer Science CarnegieMellon University Pittsburgh, PA 15213, 1996.
6. V.P. Il�in, Mathematical Modeling. Part I. Continuous and Discrete Models. Novosibirsk: SBRAS Publ., 2017.
Programmed cell deathregulation usingrationally designedmolecular probes
N. V. Ivanisenko
Institute of Cytology and Genetics SB RAS
Email: ivanisenko@bionet.nsc.ru
DOI 10.24412/cl.35065.2021.1.02.44
There are two types of apoptosis induction: intrinsic.mediated via mitochondria and extrinsic.mediated
via death receptor (DR) activation. CD95/Fas is one of the most studied members of the DR family. Theinduction
of apoptosis via CD95 is largely controlled by the Death.Inducing Signaling Complex (DISC), which is
formed upon CD95 stimulation. The major components of the DISC complex include CD95, FADD, procaspases.
8/10 and c.FLIP (cellular FLICE inhibitory protein) proteins. Deregulation of the CD95 pathway accompanies a
variety of tumors and neurodegenerative diseases. Structural modeling of the key components of the DISC
complex and in silico screening of compounds targeting them have a great potential towards design of new
therapeutics and providing deep insights into molecular mechanisms of the signaling pathway functioning and
pathology development.
In the current study we applied structural modeling and virtual screening techniques of large databases of
chemical compounds to target the caspase.8/c.FLIPL complex. Designed chemical probe FLIPinB.�was able to
target the heterodimerization interface leading to allosteric activation of the pro.apoptotic activity of the
complex. Kinetic mathematical model was further developed to analyze the observed effects of FLIPinB.�on
DISC activation. Based on the modeling results we could predict that the stabilized FLIPinB./caspase.8/c.FLIPL
complex plays a major role at the very initial stages of the DISC assembly and procaspase.8 processing.Fur.
thermore, conducted structural analysis of the DISC complex suggests high therapeutic potential of c.FLIP targeting
compounds to enhance cell death in cancer cell lines that are characterized by high c.FLIP levels.
This work was supported by the Kurchatov Genomics Center of the Institute of Cytology & Genetics SB RAS (project
number:���075.15.2019.1662).
Mesh conservation laws in filtration problems with discontinues solutions
M. I. Ivanov1, I. A. Kremer1,2, Yu. M. Laevsky1,2
1Institute of Computational Mathematics and Mathematical Geophysics SB RAS
2Novosibirsk State University
Email: laev@labchem.sscc.ru
DOI 10.24412/cl.35065.2021.1.00.21
We proposed new efficient computational algorithms for solving a number of filtration problems for a
two.phase fluid in porous and fractured.porous media. Main feature of the considered problems is in the
presence of discontinuous solutions which prohibits consideration of the mathematical modelin the form of a
system of differential equations in the entire computational domain. We have considered a model in the form
of integral laws of mass conservation and momentum in arbitrary subdomains. In particular, we formulated
Darcy's law in a generalized form for the total velocity, and the phase velocities are given by the product of the
total velocity with some functions that are discontinuous in general [1]. The resulting problem formulation
