The Protein Folding Problem: The Role of Theory

The protein folding problem was first articulated as question of how order arose from disorder in proteins: How did the various native structures of proteins arise from interatomic driving forces encoded within their amino acid sequences, and how did they fold so fast? These matters have now been largely resolved by theory and statistical mechanics combined with experiments. There are general principles. Chain randomness is overcome by solvation-based codes. And in the needle-in-a-haystack metaphor, native states are found efficiently because protein haystacks (conformational ensembles) are funnel-shaped. Order-disorder theory has now grown to encompass a large swath of protein physical science across biology. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The protein folding problem has been largely resolved through a combination of theory and experiments, leading to general principles such as overcoming chain randomness with solvation-based codes and efficiently finding native states due to the funnel-shaped conformational ensembles of proteins. Order-disorder theory now encompasses a large swath of protein physical science across biology.