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The Perturbed Free‐Energy Landscape: Linking Ligand Binding to Biomolecular Folding
Author(s) -
Abdelsattar Abdallah S.,
Mansour Youssef,
Aboulela Fareed
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000695
Subject(s) - energy landscape , ligand (biochemistry) , folding (dsp implementation) , population , biophysics , chemistry , molecular dynamics , computational biology , physics , computational chemistry , biology , biochemistry , engineering , receptor , demography , sociology , electrical engineering
The effects of ligand binding on biomolecular conformation are crucial in drug design, enzyme mechanisms, the regulation of gene expression, and other biological processes. Descriptive models such as “lock and key”, “induced fit”, and “conformation selection” are common ways to interpret such interactions. Another historical model, linked equilibria, proposes that the free‐energy landscape (FEL) is perturbed by the addition of ligand binding energy for the bound population of biomolecules. This principle leads to a unified, quantitative theory of ligand‐induced conformation change, building upon the FEL concept. We call the map of binding free energy over biomolecular conformational space the “binding affinity landscape” (BAL). The perturbed FEL predicts/explains ligand‐induced conformational changes conforming to all common descriptive models. We review recent experimental and computational studies that exemplify the perturbed FEL, with emphasis on RNA. This way of understanding ligand‐induced conformation dynamics motivates new experimental and theoretical approaches to ligand design, structural biology and systems biology.