ns/ps fast dynamics and relaxation

• Conformational changes in protein structure are separated by “energy barriers” - i.e. the energetic change necessary to go between conformational states.
• The time taken to overcome the energy barrier to go between conformational states can be separated into categories
• Most proteins have at least one interacting partner - another protein with which they interact
• Proteins that have more than one interacting partner are said to have "biomolecular promiscuity"
• In the ns/ps dynamics range is protein vibration - the collective oscillation of the protein - and protein libration - the random oscillations of the protein due to thermal energy
• Studying protein vibration and libration is important for drug design, as they affect binding affinity and kinetics of drug molecules
• Transverse magnetisation = when the net magnetic moment is in the x/y plane. Achieved when the radiofrequency pulse is applied to nuclei that are spinning parallel to the z axis.
• Longitudinal magnetisation = when the net magnetic moment is in the z axis
• Relaxation = process by which nuclear spins return to equilibria i.e. the nuclear spins are aligned with the z axis - this is their energy minima!
• Two events must happen for relaxation to occur:

  • Longitudinal relaxation - restores Mz at a rate of R1 (R1 = 1/T1). Nuclei align with the z axis.
  • Transverse relaxation - fades out of Mxy at a rate of R2 (R2 = 1/T2). Nuclei move out of the xy plane
• During NMR relaxation, small proteins have long T2, short T1 (so faster R1, slower R2)
• During NMR relaxation, large proteins have short T2, long T1 (so slower R1, faster R2)
• Relaxation is caused by time-dependent fluctuations in the local magnetic field - therefore related to protein dynamics
• Larger proteins have shorter relaxation times due to increased molecular motions, enhanced interactions and enhanced dipole-dipole coupling