Steve Corcelli

Professor of Chemistry & Biochemistry


373 Nieuwland Science Hall

Research Cluster

Computational Models

DNA Hydration Dynamics

Time-dependent Stokes shift (TDSS) experiments measure the collective dynamics of a molecular environment responding to the electronic excitation of a fluorescent probe molecule. TDSS measurements in biomolecular contexts have revealed dynamics on time scales ranging from femtoseconds to tens of nanoseconds whose physical interpretation is controversial. Some have maintained that the experiments are reporting on anomalously slow hydration dynamics, while others suggest that the slower timescales are due to biomolecular motions. We conducted a systematic computational investigation to connect experimentally measured solvation dynamics responses to specific microscopic motions of a DNA dodecamer. We modeled two different systems, a minor groove binding dye, Hoechst 33258, and coumarin 102, which replaces a natural base pair. We collected multiple molecular dynamics simulations for each probe, modeled free in solution and bound to DNA (over 2.3 microseconds in total, and calculated the TDSS response in addition to information on water rotation and translation, DNA structure and dynamics, and counterion distribution. The calculations showed unambiguously that the anomalously slow dynamics in TDSS experiments are due to specific motions of DNA. This is a radical departure from previous interpretations that focused on hydration dynamics, but one which will catalyze the use of TDSS measurements to characterize biomolecular dynamics on time scales that are inaccessible to other techniques. This contribution also illustrates how theory and simulation can substantially increase our understanding of experimental measurements.


  1. "DNA Minor-Groove Binder Hoechst 33258 Destabilizes Base-Pairing Adjacent to its Binding Site" Zhang, X.-X.; Brantley, S.L.; Corcelli, S.A.; Tokmakoff, A. Commun. Biol. 2020, 3, 525. DOI:
  2. "Dynamically Driven Allostery in MHC Proteins: Peptide-Dependent Tuning of Class I MHC Global Flexibility" Ayres, C.M.; Abualrous, E.T.; Bailey, A.; Abraham, C.; Hellman, L.M.; Corcelli, S.A.; Noé, F.; Elliott, T.; Baker, B.M. Front. Immunol. 2019, 10(May), 966. DOI:10.3389/fimmu.2019.00966
  3. "Peptide and Peptide-Dependent Motions in MHC Proteins: Biophysical Underpinnings and Immunological Implications" Ayres, C.M.; Corcelli, S.A.; Baker, B.M. Front. Immunol. 2017, 8, 935.
  4. "Modeling Peptide Fluctuations in Immunologic Recognition" Ayres, C.M.; Riley, T.P.; Corcelli, S.A.; Baker, B.M. J. Chem. Inf. Model. 2017, 57, 1990.