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A Computational Perspective to Intermolecular Interactions and the Role of the Solvent on Regulating Protein Properties

Joel Mieres‐Pérez, Yasser Almeida‐Hernández, Wolfram Sander, Elsa Sánchez‐García

2025Chemical Reviews12 citationsDOIOpen Access PDF

Abstract

Intermolecular interactions play a key role in determining and tuning the structure and function of proteins. Following a simplified conventional scheme, molecular interactions are often classified as strong (long-range), typically driven by ionic contacts and salt bridges, or as weak (short-range), such as hydrophobic interactions. The reality is more complex, with classical strong interactions having weak contributions and vice versa. The interaction network regulating the properties of biomolecular systems such as proteins and their media goes beyond a single sort of contribution, and instead it is characterized by the interplay between several forces of diverse nature. In this review, we discuss, via selected examples, state of the art methodologies and applications of computational techniques to explore the role of intermolecular interactions, with emphasis on solvent effects on protein folding, enzymatic activity, and protein-peptide binding.

Topics & Concepts

ChemistryIntermolecular forceChemical physicsFolding (DSP implementation)Hydrophobic effectFunction (biology)Protein–protein interactionProtein foldingIntermolecular interactionIonic bondingComputational chemistryNanotechnologyMoleculeIonBiochemistryOrganic chemistryElectrical engineeringBiologyMaterials scienceEvolutionary biologyEngineeringProtein Structure and DynamicsComputational Drug Discovery MethodsEnzyme Structure and Function