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SUMMARY:Generative modelling for protein evolution and design
DTSTART;VALUE=DATE-TIME:20250611T093000Z
DTEND;VALUE=DATE-TIME:20250611T100000Z
DTSTAMP;VALUE=DATE-TIME:20260608T174740Z
UID:indico-contribution-1538@cern.ch
DESCRIPTION:Speakers: Francesco Zamponi (Sapienza Università di Roma)\nPr
 otein fitness landscapes frequently exhibit epistasis\, where the effect o
 f a mutation depends on the genetic context\, i.e.\, the rest of the prote
 in sequence. Epistasis increases landscape complexity\, often resulting in
  multiple fitness peaks. In its simplest form\, known as global epistasis\
 , fitness is modeled as a non-linear function of an underlying additive tr
 ait. In contrast\, more complex epistasis arises from a network of (pairwi
 se or many-body) interactions between residues\, which cannot be removed b
 y a single non-linear transformation. Recent studies have explored how glo
 bal and network epistasis contribute to the emergence of functional bottle
 necks - fitness landscape topologies where two broad high-fitness basins\,
  representing distinct phenotypes\, are separated by a bottleneck that can
  only be crossed via one or a few mutational paths. I will introduce and a
 nalyze a simple model of global epistasis with an additive underlying trai
 t\, and demonstrate that functional bottlenecks arise with high probabilit
 y if the model is properly calibrated. These results underscore the necess
 ity of sufficient heterogeneity in mutational effects for the emergence of
  functional bottlenecks. Moreover\, the model agrees with experimental fin
 dings\, at least in small enough combinatorial mutational spaces.\n\nhttps
 ://indico.unina.it/event/91/contributions/1538/
LOCATION:Hotel Palazzo Alabardieri Sala Caracciolo
URL:https://indico.unina.it/event/91/contributions/1538/
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