Evolutionary Switches Structural Transitions via Coarse-Grained Models

Francesco Delfino, Yuri Porozov, Eugene Stepanov, Gaik Tamazian, Valentina Tozzini

Результат исследований: Научные публикации в периодических изданияхстатья

Аннотация

Transitions between different conformational states are ubiquitous in proteins. A vast class of conformation-changing proteins includes evolutionary switches, which vary their conformation as an effect of few mutations or weak environmental variations. However, modeling those processes is extremely difficult due to the need of efficiently exploring a vast conformational space to look for the actual transition path. In this study, we report a strategy that simplifies this task attacking the complexity on several sides. We first apply a minimalist coarse-grained model to the protein, based on an empirical force field with a partial structural bias toward one or both the reference structures. We then explore the transition paths by means of stochastic molecular dynamics and select representative structures by means of a principal path-based clustering algorithm. We finally compare this trajectory with that produced by independent methods adopting a morphing-oriented approach. Our analysis indicates that the minimalist model returns trajectories capable of exploring intermediate states with physical meaning, retaining a very low computational cost, which can allow systematic and extensive exploration of the multistable proteins transition pathways.

Язык оригиналаанглийский
Страницы (с-по)189-199
Число страниц11
ЖурналJournal of Computational Biology
Том27
Номер выпуска2
Ранняя дата в режиме онлайн26 ноя 2019
DOI
СостояниеОпубликовано - 6 фев 2020

Предметные области Scopus

  • Моделирование и симуляция
  • Молекулярная биология
  • Генетика
  • Вычислительная математика
  • Математика и теория расчета

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