1. Biological Water, Protein Structure and the Dynamical Transition
Yunfen He and Andrea Markelz
Department of Physics, University at Buffalo, SUNY
PRF AC6
NSF CAREER PHY

2. The “Protein Dynamical Transition”
Applying THz to an Outstanding Biomolecular Question
The “Protein Dynamical Transition”
D. Ringe and G. A. Petsko, Biophysical Chemistry 105 (2003)
Ribonuclease A
Roh, J.H. et al., Biophys J, (2006) 91,
The requirement of minimum hydration level suggests the rapid increase in flexibility arises from a change in the dynamics of the solvent in direct contact with the biological molecule, the biological water.

3. interfacial water & bulk water
Samir Kumar Pal and Ahmed H. Zewail, Chemical Reviews, 2004, Vol. 104, No

4. What is the Dynamical Transition?
Solvent mediated diffusive motions:
solvent slaved motions
Activated side chain motions
Activated solvent motions
Transition in solvent dynamics

5. Strong Glass Fragile Glass
Observation of fragile-to-strong dynamic crossover in protein hydration water
S.-H. Chen, L. Liu, E. Fratini, P. Baglioni, A. Faraone, and E. Mamontov
Proceedings of National Academy of Sciences of America, 9012–9016 June 13,
Strong Glass
Fragile Glass
EQUATIONS FOR FRAGILE ---VFT, AND STRONG ---ARRHENIUS …ROLE OF CONFINEMENT…PICTURE OF PROTEIN SURFACE WITH WATER…

6. 1BWH.PDB
Neutron Scattering Investigations Of Proton Dynamics Of Water And Hydroxyl Species In Confined Geometries
S.-H. Chen and C.-K. Loong
Nuclear Engineering And Technology, VOL.38 NO.3 APRIL
EQUATIONS FOR FRAGILE ---VFT, AND STRONG ---ARRHENIUS …ROLE OF CONFINEMENT…PICTURE OF PROTEIN SURFACE WITH WATER…

7. Does Structure Play a Role in the Dynamical Transition?
EQUATIONS FOR FRAGILE ---VFT, AND STRONG ---ARRHENIUS …ROLE OF CONFINEMENT…PICTURE OF PROTEIN SURFACE WITH WATER…
Does Structure Play a Role in the Dynamical Transition?

8. Terahertz dielectric response is sensitive to the transition
MOST MEASUREMENTS USE NEUTRON…LARGE SAMPLE REQUIREMENTS (~100MG) AND CAREFUL DEUTERATION
THZ DIELECTRIC RESPONSE TABLE TOP MEASUREMENT WITH SMALLER SAMPLE REQUIREMENT (~1 MG)
A. Markelz et al. Chemical Physics Letters 442 (2007) 413–417

9. Terahertz Time Domain Spectroscopy (THz TDS)
Solution cell
EMPHASIZE ALL MEASUREMENTS IN SOLUTION, EQUATION FOR DIELECTRIC RESPONSE…
g(w): density of states; f(w): oscillator strength; g(w): damping coefficient;
h(t): distribution of relaxation times

10. Net increase in low frequency response with denaturing
EXPLANATION OF WHY MIGHT EXPECT INCREASE
-KARPLUS CALCULATION
-HUNT KERR MEASUREMENTS
POSSIBLE CONTRIBUTIONS
-RED SHIFTING OF MODES WITH LOSS OF STRUCTURE—KARPLUS
-INCREASE IN SIDE CHAIN EXPOSURE RESULTS IN INCREASE IN RELAXATIONAL CONTRIBUTION
-NOT THE SAME RESULT AS SUGGESTED BY MET/H20 DENATURING IN HUNT ET AL, BUT INAGREEMENT WITH THERMAL DENATURING OF HUNT.

11. Terahertz Dielectric response
Herman W. T. van Vlijmen and Martin Karplus, J. Phys. Chem. B 1999, 103,

12. Protein structure is not necessary for dynamical transition (HEWL)
NOTE THAT ALL THZ MEASUREMENTS OF DYNAMICAL TRANSITION FOR NATIVE SOLUTIONS DO NOT SHOW CLEAR TRANSITION IN INDEX, HOWEVER HYDRATED POWDER MEASUREMENTS DO SHOW TRANSITION… “BULK” SOLVENT INDEX TEMPERATURE DEPENDENCE DOMINATES AS WILL BE DISCUSSED IN LATER TALK.

13. Protein structure is not necessary for dynamical transition (random coil poly-L-lysine)
NOTE THAT ALL THZ MEASUREMENTS OF DYNAMICAL TRANSITION FOR NATIVE SOLUTIONS DO NOT SHOW CLEAR TRANSITION IN INDEX, HOWEVER HYDRATED POWDER MEASUREMENTS DO SHOW TRANSITION… “BULK” SOLVENT INDEX TEMPERATURE DEPENDENCE DOMINATES AS WILL BE DISCUSSED IN LATER TALK.

14. Molecular dynamics simulation
COULD THE LACK OF DYNAMICAL TRANSITION IN DIMER AND TRIMER BE DUE TO LESS NET BIOWATER, TRANSITION CONTRIBUTION TO TOTAL SIGNAL BELOW SIGNAL TO NOISE.
-MOLAR CONCENTRATION HIGHER FOR DIMER AND TRIMER
TABLE OF MOLAR CONCENTRATIONS….NET BIO WATER ACTUALLY GREATER FOR THESE
-MD SIMULATIONS DIRECTLY EXAMINING DYNAMICS OF INDIVIDUAL PROTEIN, BACKGROUND FREE
SHOW THAT INDEED FOR HYDRATED SMALL ALPHA HELIX TRANSITION OCCURS, BUT FOR STRUCTURE FREE HYDRATED TRIMER TRANSITION ABSENT

15. Solvent or side chain diffusive motions??
Data do not support Fragile to Strong transition
Arrhenius Temperature dependence only
No structural dependence
The dynamical transition is caused by activated diffusive motions!!
Solvent or side chain diffusive motions??

16. Chain length dependence of dynamical transition

17. What causes the dynamical transition?
Activated diffusive motions of adjacent solvent responsible for dynamical transition.
Apparent minimum chain length required for dynamical transition.
The temperature dependence of the diffusive motions is the result of the polypeptide on the dynamics of biological water.
SHOW ARRENHIUS PLOT --- NO SIGN OF VTF TEMPERATURE DEPENDENCE…POSSIBLE THAT THZ SIGNAL DOMINATED BY PROTEIN AND NOT SHOWING TRUE TEMPERATURE DEPENDENCE OF SOLVENT…BUT IN AGREEMENT WITH SOKOLOV’S GROUP LOW FREQUENCY (KHZ????) DIELECTRIC MEASUREMENTS.
When this dynamic crossover occurs, the biological water changes from the “more fluid” high-density liquid form (which induces the protein to adopt more flexible conformational substates) to the “less fluid” low-density liquid structure (which induces the protein to adopt more rigid conformational substates).
The dynamical transition does not require a protein!!

18. Thanks
&
Questions?