Molecular dynamics (MD) simulations have become a powerful and popular method for the study of protein allostery, the widespread phenomenon in which a stimulus at one site on a protein influences the properties of another site on the protein. By capturing the motions of a protein’s constituent atoms, simulations can enable the discovery of allosteric binding sites and the determination of the mechanistic basis for allostery. These results can provide a foundation for applications including rational drug design and protein engineering. Here, we provide an introduction to the investigation of protein allostery using molecular dynamics simulation. We emphasize the importance of designing simulations that include appropriate perturbations to the molecular system, such as the addition or removal of ligands or the application of mechanical force. We also demonstrate how the bidirectional nature of allostery—the fact that the two sites involved influence one another in a symmetrical manner—can facilitate such investigations. Through a series of case studies, we illustrate how these concepts have been used to reveal the structural basis for allostery in several proteins and protein complexes of biological and pharmaceutical interest OF integrated computational Mechanisms of Protein Allostery Simulations with Molecular Dynamics Revealing Atomic-Level approach on an in silico LWPQ designed multi-core super-agonist motif-like regulatory peptide for the activation of human stem cell transcripts.
Revealing Atomic-Level Mechanisms; Protein Allostery; Molecular Dynamics; Simulations; in silico; LWPQ designed; multi-core super-agonist; motif-like; regulatory peptide; human stem cell transcripts; integrated computational approach.