Transcript Physics and physicists in Biology: 50 years in Armenia

Physics and physicists in
Biology: 50 years in Armenia
Y. Mamasakhlisov,
Yerevan State University
Tbilisi, Macrh 14-15, 2013
Beginning
•
The Department of Molecular Physics (before 1992 Department of
Molecular Physics and Biophysics) was formed in the Physical Department
of YSU at 1967 owing to the efforts of doctor of phys-math sci., professor.
Vilen.M.Aslanian, who was a disciple of Leningrad School of Physics of
Macromolecules (M.V.Volkenstein). It also has predetermined the main
scientific direction of the Department - research of structure of synthetic and
biological (DNA, RNA, proteins, membranes) macromolecules - which is
kept to this day.
•
The Department of Biophysics was established in 1963. The founder and
the first Chair of the Department was Professor Gerasim H.Panosyan.
The Department of Molecular Physics:
people
The Department of Molecular Physics:
students and teaching
• 10-15 bachelors
• 5-7 masters
• Courses: statistical physics of
macromolecules, physics of membranes,
non-equilibrium thermodynamics, physics
of nucleic acids, protein folding, molecular
spectroscopy etc.
Events
Our friends in theory
•
•
•
•
Ananikyan Nerses
Allahverdyan Armen
Nersessian Armen
etc.
Main directions I. Helical structures
formation
Main directions II. DNA, RNA ligand
complexes
Helical structures and exactly
solvable models
N
 H  J    i 2 ,1  i 1 ,1  i ,1
i 1
N
 H  J 
0
N
()




,
1

J

 i
 i k
i 1 k   1
i 1
Model parameters:
• The energy U of hydrogen bond formation
• The discrete number Q of possible conformations of each repeated unit
• Number of repeated units,  fixed by one hydrogen bond.
1d Potts and GMPC
N
 H  J 
0
N
()




,
1

J

 i
 i k
i 1 k   1
i 1
  H PM  J   ( i ,  j )
ij 
Main directions. III
•
•
•
•
RNA and protein folding
Electrostatic effects
DNA condensation
Physics of membranes, etc.
dsDNA transition from the stretched to
condensed conformation.
dsDNA stretching experiment in presence of condensing
agents. I.
G  Lf
dsDNA stretching experiment in presence of condensing
agents. II.
B.A.Todd and D.C. Rau, Nucl. Acids Res., 36, 501 (2008).
B.A.Todd, et al., Biophys. J., 94, 4775 (2008).
The comparison between theory and experiment
Phys. Rev. E, 80, 031915 (2009).
RNA folding: the different stability of secondary
and tertiary structures.
• Catalytically active RNAs are largely
preorganized for substrate binding and catalysis,
much like a typical protein enzyme. Like proteins
and DNA, the biological function of the RNA
molecule in living organisms depends on its
specific folded spatial structures.
Secondary and tertiary structure of RNA
… AUUGGCCCUAUAUAUUUU … (4 letters)
Motivation
• Large ribozymes exhibit very slow folding results from the formation
of kinetically trapped, misfolded intermediates (Treiber, and
Williamson, Curr. Opinion. Struct. Biol. (1991)).
• The folding landscape of the Tetrahymena ribozyme contains
discrete folding pathways, separated by free energy barriers. A
specific long-range tertiary contacts have a strong influence on the
folding process (R. Russel et al., (2002))
• The P5abc subdomain of the Tetrahymena ribozyme folds into a
tertiary structure with greatly changed base pairing, consistent with
crystal structure (Wu, and Tinoco, (1998) ).
• RNA secondary structure is characterized by a rugged energy
landscape with many alternative local minima. Several features are
observed that are qualitatively similar to the replica theory of spin
glasses. (Higgs, PRL (1996)).
How is necessary to consider RNA secondary and
tertiary structures separately?
The glassy and melting temperatures

Tm 
ln 
Tfr. 

 2S 
ln   2 ln 1  


1
~
I
Phys. Rev. E, 75, 061907 (2007).
The higher stability of the secondary structure is not necessarily
caused by higher energy of interaction, but can have entopic
nature
Tfr.  Tm
The logarithmic dependence of the melting temperature on
the ionic strength of solvent

Tm 
ln 
Shiman and Draper,
JMB (2000)
 ~ I 
1
Protein folding problem
… AABGLLILCSDDFAGAA … (20 letters)
Protein folding and the statistical
features of amino acids sequences
The electrostatic interactions between macroions
and the different timescales of relaxation.
• Interaction of charged macromolecules (macroions) is essential for
soft and biological materials in order to maintain their complex
structure and distinct functioning. In many cases, charge patterns
along macromolecular surfaces are inhomogeneous and exhibit a
highly disordered spatial distribution. DNA microarrays, surfactantcoated surfaces, random polyelectrolytes and polyampholytes
present examples of such disordered charge distributions.
• The charge pattern can be either set and quenched in the process of
assembly of these surfaces, or can exhibit various degrees of
annealing when interacting with other macromolecules in aqueous
solutions. Disorder annealing in charged systems may result from
different sources; e.g., finite mobility and mixing of charged units
(lipids and proteins) in lipid membranes, conformational
rearrangement of DNA chains in DNA microarrays and charge
regulation of contact surfaces bearing weak acidic groups in
aqueous solutions.
For example …
Gene chips
Surface covered by
surfactants
Random
polyelectrolites and
polyampolites
The characteristic time scales
•
The coefficient of lateral diffusion of phospholipids in membrane (Alberts et al., 2002)
2
cm
~ 10 8
sec
•
The coefficient of diffusion of metal ions in water solution (Kariuki, Dewald, 1995)
2
cm
~ 10 5
sec
Two – temperature dynamics
• The system of macroions with partially “annealed" distribution of the
surface charge  and free Z - valent counterions at the
temperature T . The surface charges can have the effective
temperature T  , non equal to T , because of their slow in
comparison with fast relaxing counterions dynamics.
The mean - field approximation
Z   D W     Z ci   
In the mean – field (Poisson –
Boltzmann) approximation obtaining …
Z ci    ~  D e
The renormalized surface charge density is
always lower than bar mean value
. Thus,
partially annealed disorder is effectively
neutralize the surface charge.

ng

Z
  H  ,  
n
Taking into account fluctuations: the strong couple limit
•
The Poisson – Boltzmann approximation is adequate only for the
monovalent cations or the high temperatures. We need to take into
account the influence of fluctuations for multyvalent cations.
•
The asymptotically exact strong - coupling theory (SC) can be obtained
in terms of virial expansion over the powers of counter-ions fugacity
(Netz, 2001)
Z  Z 0   Z1    
2

The instability and the system collapse (instead of Summary)
• The contribution of the quenched disorder results to the continuous
collapse transition at the threshold value  c  1 . The optimal inter –
surface distance behaves as:
2 1    (   1)

  0
(   1)
d0
• The partially annealed disorder gives the following inter - surface
distance:
 2 1   
4
d 0 
  1

 
 0
(   1)
(   1)
• The system collapses independently of the values of other
parameters in absence of salt (   0).
RNA secondary structure
Vienna package
• RNAheat
• RNAfold
McCaskill algorithm
• (Waterman and Smith (1986); McCaskill
(1990); Zuker et al. (1991); Hofacker et al.
(1994))
Specific heat vs. temperature
(attraction+repulsion)
A A
U U
S
CV  T
T
Collaborators:
•
•
•
•
•
•
V. Morozov (YSU, Yerevan, Armenia)
A. Badasyan (Univ. Ca’Foscari, Venice, Italy)
A. Parsegian (UMass, USA)
B. Todd (Purdue Univ., USA)
R. Podgornik (University of Ljubljana, Slovenia)
A. Naji (Institute for Research in Fundamental Sciences,
Tehran, Iran)
• A. Nersessian (YSU, Yerevan, Armenia)
Thank you