Eunkyung Kim^1,8, Sanghwa Lee^2,3,8, Aram Jeon^4,5, Jung Min Choi¹, Hee-Seung Lee^4,5, Sungchul Hohng^2,3,6* & Hak-Sung Kim^1,7*

¹Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea. ²Department of Physics and Astronomy, Seoul National University, Seoul, Korea. ³National Center for Creative Research Initiatives, Seoul National University, Seoul, Korea. ⁴Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Korea. ⁵Molecular-Level Interface Research Center, Korea Advanced Institute of Science and Technology, Daejeon, Korea. ⁶Biophysics and Chemical Biology, Seoul National University, Seoul, Korea. ⁷Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon, Korea. ⁸These authors contributed equally to this work.

^*Correspondence to: Sungchul Hohng or Hak-Sung Kim
 
Abstract
Protein dynamics have been suggested to have a crucial role in biomolecular recognition, but the precise molecular mechanisms remain unclear. Herein, we performed single-molecule fluorescence resonance energy transfer measurements for wild-type maltose-binding protein (MBP) and its variants to demonstrate the interplay of conformational dynamics and molecular recognition. Kinetic analysis provided direct evidence that MBP recognizes a ligand through an 'induced-fit' mechanism, not through the generally proposed selection mechanism for proteins with conformational dynamics such as MBP. Our results indicated that the mere presence of intrinsic dynamics is insufficient for a 'selection' mechanism. An energetic analysis of ligand binding implicated the critical role of conformational dynamics in facilitating a structural change that occurs upon ligand binding.