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Coevolution and epistasis in antibiotic-resistant beta- lactamases

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Coevolution and epistasis in antibiotic-resistant beta- lactamases

Author: Rodriguez-Rivas, Juan
Publisher: Barcelona Supercomputing Center
Year: 2019
Source: https://upcommons.upc.edu/bitstream/2117/171448/1/40_Coevolution_and_epistasis.pdf
100
Se e o Ochoa Resea ch Semina - BSC
2018-2019
July 2nd, 2019
Coe olu ion and epis asis in an ibio ic- esis an be a-
lac amases
Juan Rod iguez-Ri as
BSC, Spain
Abs ac
The e ec o mu a ions depends on he con ex whe e hey appea due o
epis a ic in e ac ions. Fo ins ance, a mu a ion can be neu al only i ano he
speci ic mu a ion has occu ed p e iously, and de imen al o he wise.
Simila ly, om a long- e m e olu iona y pe spec i e, a mu a ion can be
de imen al in a p o ein bu no in a homologous p o ein due o hei di e ences
in amino acids, e en i hey pe o m he same cellula unc ion. The
appea ance o deep mu a ional scanning echniques in ecen imes, ha
allows esea ches o measu e he e ec o ens o housands o e en
hund eds o housands o combina ions o mu a ions, ha e inally pe mi ed
sys ema ic s udies o epis asis in p o eins. A he same ime, he e ha e been
b eak h ough imp o emen s on he compu a ional modeling o coe olu ion in
p o eins, i.e. he in e dependencies be ween posi ions, ha a ise om
epis a ic in e ac ions coming om unc ional and s uc u al cons ain s ha a e
p esen in e e y p o ein. Du ing his collabo a ion wi h he S a is ical
Genomics and Biological Physics g oup o he So bonne Uni e si y o Pa is,
we ha e combined bo h compu a ional models and expe imen al da a o
un eil he unc ional and s uc u al cons ain s a e p esen and shapes he
e olu iona y pa hs o be a-lac amases, an impo an amily o an ibio ic-
esis an p o eins. We a e able o de ec and cha ac e ized cons ain s in be a-
lac amases coming om epis a ic in e ac ions and hei dependency on he
con ex . These esul s p o ide insigh s in o he unc ion and e olu ion and
be a-lac amases, and could be use ul o he de elopmen o new an ibio ics
and agains he eme gence o an ibio ic esis ance.
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Se e o Ochoa Resea ch Semina - BSC
2018-2019
Sho bio
Juan Rod iguez-Ri as is cu en ly inishing his PhD
deg ee in compu a ional biology a he
Compu a ional Biology g oup a BSC. Du ing his
PhD, he has s udied coe olu ion wi hin and
be ween p o eins, a ield o s udy a he in e ace
be ween p o ein sequences and s uc u es.
P e iously he wo ked in so wa e de elopmen and
deploymen in he p i a e sec o . His o mal aining
comp ises Compu e Science (Uni e si y o
Se ille), Bioin o ma ics and Compu a ional Biology (Complu ense Uni e si y o
Mad id) and Biophysics (Au onomous Uni e si y o Mad id).