long-range allosteric effect i n gene transcriptional regulat ion Ming Li Graduate School, CAS Zhong-can Ou-yang Institute of Theoretical Physics, CAS International Symposium on the Recent Progress in Quantitative and Systems Biology , Dec 9-11, The Chinese University of Hong Kong
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Long-range allosteric effect in gene transcriptional regulation Ming Li Graduate School, CAS Zhong-can Ou-yang Institute of Theoretical Physics, CAS International.
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long-range allosteric effect in gene transcriptional regulation
Ming LiGraduate School, CAS
Zhong-can Ou-yangInstitute of Theoretical Physics, CAS
International Symposium on the Recent Progress in Quantitative and Systems Biology , Dec 9-11, The Chinese University of Hong Kong
Outline
Stressed state of DNA in vivo
Model of topologically constrained DNA and duplex separation
Long-range Allosteric Effect and Database investigation: a case study
Part I
Stressed state of DNA in vivo
4 types of nucleotides: Adenine, ThymineGuanine, Cytosine
Topological constraint long-range coupling between any two sites ! twisting energy of the two strands in bubble regions
unpairing energy in bubble (sequence dependent ) nucleation (initiation) energy for bubble formation (there can be multiple bubbles on a single DNA)
4321 HHHHH
21 2
1( )
2
qRT nH
A
j
jjnc
H 22 2
j
jjbnH 3
j
jj nnaarH )1( 14
8.10a 1molkcal
58.3c 21 radmolkcal
255.0ATb 1molkcal
301.1GCb 1molkcal
Parameter (illustrative) values under physiological condition
(the qualitative results shown later are actually quite insensitive to those values )
Unwounding Probability Profile
{ }
{ }
( 1)Hj
sj H
s
e n
pe
for any DNA sequence
Pi and Pj are tightly correlated due to the global topological constraints ( H1 !) imposed on the dsDNA, i.e., bubbles can be competitive in releasing the imposed twisting stress.
Can there be anything new (besides the individual denaturing events) introduced by topological constraints ? Long-range Allosteric Effect : the tele-communication between site A and B(protein binding onto the denatured site A may re-close the bubble and induce a new bubble at site B)
A
B
(DNA)
(protein)
B
A
It’s difficult to detect such a phenomenon in vivo by experiments, and it’s also almost impossible to directly ‘calculate’ such an effect quantitatively for real cases by taking account of every molecular detail (one can be drown in the details).
Beginning with everything , ending with nothing !
Anyway, How can one do anything meaningful ? --- Bioinformatics to rescue !
Bioinformatics offers an alternative approach:exploring the biological data to find the statistically significant patterns which may cast some light on the understanding of the underlying molecular mechanism
Part III
Long-range Allosteric Effect and Database investigation: a (bioinformatic) case study on SMAR function