title: Single molecule insights on conformational selection and induced fit mechanism.
abstract: Biomolecular interactions regulate a plethora of vital cellular processes, including signal transduction, metabolism, catalysis and gene regulation. Regulation is encoded in the molecular properties of the constituent proteins; distinct conformations correspond to different functional outcomes. To describe the molecular basis of this behavior, two main mechanisms have been advanced: 'induced fit' and 'conformational selection'. Our understanding of these models relies primarily on NMR, computational studies and kinetic measurements. These techniques report the average behavior of a large ensemble of unsynchronized molecules, often masking intrinsic dynamic behavior of proteins and biologically significant transient intermediates. Single molecule measurements are emerging as a powerful tool for characterizing protein function. They offer the direct observation and quantification of the activity, abundance and lifetime of multiple states and transient intermediates in the energy landscape, that are typically averaged out in non-synchronized ensemble measurements. Here we survey new insights from single molecule studies that advance our understanding of the molecular mechanisms underlying biomolecular recognition.
authors.affiliation: Bio-Nanotechnology Laboratory, Department of Chemistry, Nano-Science Center, Lundbeck Foundation Center Biomembranes in Nanomedicine, University of Copenhagen, 2100 Copenhagen, Denmark. Electronic address: hatzakis@nano.ku.dk.
authors.forename: Nikos S
authors.initials: NS
authors.lastname: Hatzakis
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D011506:Proteins
keywords: Allosteric regulation; Conformational selection; De novo protein synthesis; In silico drug design; Induced fit; Single enzyme