|
|
VSEOLOD KATRITCH |
Geometry and Physics of Knots |
Conformational Properties and Force-extension Characteristics of Chromatin
Fibers |
Structural Modeling of Nucleic Acids-Drug Interaction |
The first project, started in 1996, deals with so-called ideal knots
and the conformational properties of knotted polymer rings. In a recent
study, we found that the knots in a long polymer chain tend to be spontaneously
localized on a small portion of the molecule rather than spread all over
the polymer. This entropic effect is of general importance for understanding
the behavior of polymers under different conditions. A paper on the entropic
tight knotting of long circular polymers has been submitted to Physical
Review Letters for publication. |
In the second project, carried out in collaboration with Prof. Carlos
Bustamante, we built a comprehensive physical model of chromatin fiber.
The comparison between simulated and experimental force-extension characteristics
can be used to estimate the structural parameters of the chromatin fiber
under specific ionic conditions. The fiber parameters obtained in this
study are consistent with those observed by direct visualization methods
such as scanning force microscopy and cryo-electron microscopy. This work
was reported at the 42nd annual meeting of the Biophysical Society; the
manuscript has recently been accepted by the Journal of Molecular Biology. |
The third project employes ICM modeling package (Molsoft, Inc.) to study
the binding of the aminoglycoside tobramycin to double-stranded RNA, as
well as sequence specific recognition of DNA by pyrrole-imidazole containing
polyamide hairpins. Polyamide compounds use an effective base-pair recognition
code to bind the minor grove of B-DNA with affinities and specificities
comparable to native transcription factors. We have developed a comprehensive
procedure to manipulate the polyamide ́residuesî and search effectively
for the global energy minimum of the DNA-polyamide complexes. We estimate
the accuracy of the binding energy predictions to be ~1.5 kcal/mol, based
on an extensive comparison with the corresponding affinity constants measured
experimentally. This modeling system provides theoretical support for the
rational design of polyamidebased antigene drugs. The first results of
this work were reported at the 1999 PMMB meeting, and a full manuscript
will be submitted for publication in June 1999. |
|
|
