We present a specific machine learning model to predict the stability of missense mutation in TP53 using the example of a combination of several physical experiments in which the unfolding of P53 mutations was studied depending on the denaturant concentration.

The thermodynamic parameters of common missense tumorigenic and selected single suppressor mutations were determined by this calculations and compared with those of the native p53 DNA-binding domain experiments.The effect of common cancer mutations on the thermodynamic stability of wild type p53 has been well studied by urea denaturation.

Mathematical Modeling of p53 Mutations

List of calculated and experimental values ​​to which machine learning methods and clustering will be applied to develop a method for predicting the stability of mutant proteins

lg(cond(W))
Виталий Соколов
lg[Kd]
Приключения, исторический
dG(D-N)(H2O)
Россия, Норвегия, Франция
TdH
15 мая
[Urea]50%, M
Дмитрий Джибелия, Вячеслав Поронин, Евгений Луневский
ddG(D-N)(H2O)
Симеон Войнович, Лариса Марисова, Тимур Филанов, Маргарита Сотина
Thermodynamic stability of wild-type and mutant p53 core

A system for analysis of the stability of human p53 DNA-binding domain (amino acids 94–312) and its mutants

the structural effects of cancer hot spot mutations by x-ray crystallography because its higher thermodynamic stability should make it more amenable for crystallographic studies, in particular in the case of highly destabilizing mutations.
[Thermodynamic stability of wild-type and
mutant p53 core domain]
[Semirational design of active tumor suppressor p53 DNA binding domain with enhanced stability]
[Mechanism of rescue of common p53 cancer mutations by second-site suppressor mutations]
[Structures of oncogenic, suppressor and rescued p53 core-domain variants: mechanisms of mutant p53 rescue]
p53 protein denaturation curves obtained in 4 different experiments

Changes in free energy of urea-induced unfolding of p53 core domain mutants

Equilibrium denaturation of p53 core domain
Zero Block
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
table of experimental values ​​and calculated values ​​for p53 mutations

T123A
V143A
H168R
G245S
R249S
V143A/N268D
G245S/N239Y
R249S/T123A
R249S/H168RT123A/H168R
R249S/T123A/H168R
V157FV157F/N235K
V157F/N235K/N239Y
R175HIS
C242SER
R248Q
R273H
Q104P
Q104HIS
A129D
A129E
A129S
M133L
D148E
D148S
T150P
Q165K
Q165E
R174K
C182S
L201P
V203A
L206S
D228E
N239Y
S260P
N268D

p53 mutations:

N239Y/N268D
M133L/V203A
M133L/N239T/N268D
V203A/N239Y/N268D
M133L/V203A/N239Y/N268D

Effects of Mutations on the Stability of T-p53C

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p53 mutations
Q104P
Q104HIS
A129S
M133L
T150P
R174K
C182S
L201P
V203A
L206S
N239Y
S260P
N268D
Zero Block
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Zero Block
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Zero Block
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Zero Block
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Zero Block
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Zero Block
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Zero Block
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Zero Block
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Creativity is to discover a question that has never been asked. If one brings up an idiosyncratic question, the answer he gives will necessarily be unique as well.
Трейлер
О море, в прокате с 15 мая
Кадры из фильма
В ролях
  • Иван Санин
  • Сергей Палин
  • Ева Михайлова
  • Даур Масори
  • Лилиана Каро
  • Максим Иванченков
  • Карлос Лот
  • Станислав Болецкий
Рецензии прессы
Награды
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