Emergence of globular protein folds from random amino acid sequences

Eugene V. Koonin - 21.10.2025, 8:40. B7 Zoologická posluchárna, Viničná 7 - 2. patro

Source: www.natur.cuni.cz/udalosti

The origin and evolution of protein folds is a major, long-standing problem in biology, as most fold diversity arose very early in life. Realistic simulation was previously impossible but is now feasible thanks to modern structure prediction tools like AlphaFold and ESMFold.

Protein Fold Evolution Simulation (PFES), a new computational approach that simulates the evolution of globular folds from random amino acid sequences with atomistic detail iteratively introduces mutations, evaluates structure changes, and selects proteins based on a fitness landscape.

PFES simulations successfully reproduced the evolution of simple natural folds and generated novel folds. These findings offer insights into the rapid evolution of fold diversity in early life. PFES tracks the complete evolutionary history, providing a powerful platform for testing hypotheses on protein fold evolution.