Single molecule insights on conformational selection and induced fit mechanism

TY - JOUR

T1 - Single molecule insights on conformational selection and induced fit mechanism

AU - Hatzakis, Nikos

N1 - Special issue : conformational selection

PY - 2014/2

Y1 - 2014/2

N2 - 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.

AB - 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.

U2 - 10.1016/j.bpc.2013.11.003

DO - 10.1016/j.bpc.2013.11.003

M3 - Journal article

C2 - 24342874

SN - 0301-4622

VL - 186

SP - 46

EP - 54

JO - Biophysical Chemistry

JF - Biophysical Chemistry

ER -