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Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session VIII Abstracts
Sequence Variations and Allosteric Dynamics in Binding
Turkan Haliloglu
.
Bogazici University, Istanbul, Turkey.
Proteins are of highly dynamic nature with a complex interrelation between structural dynamics
and their binding behavior. With the capacity of assuming an ensemble of conformations, they
perform local to global fluctuations to interact with others in a dynamic infrastructure adopted to
functional motion. On the exemplary case studies, it will be presented how the
sequence variations at hinge regions of most cooperative movements could be instrumental to
allosterically affect the binding site dynamics or dispose alternative binding modes with a change
in functionality. The long-range dissemination of the perturbations in local chemistry or physical
interactions through an impact on global dynamics can reform the allosteric dynamics. The
findings posits an aspect for the coupling of structural dynamics and evolvability in
the modulation of protein interactions.
Extracting Dynamics Information from Multiple Molecular Structures and
Computationally Generating Their Transition Pathways
Robert Jernigan
1
, Kannan Sankar
1
, Kejue Jia
1
, Jie Liu
1
, Yuan Wang
1
, Ataur Katebi
1
, Michael
Zimmermann
2,1
.
1
Iowa State University, Ames, IA, USA,
2
Mayo Clinic College of Medicine, Rochester, MN,
USA.
Meaningful dynamics information can be extracted from multiple experimental structures of the
same, or closely related, proteins or RNAs. The covariance matrix of atom positions is
decomposable into principal components. Usually only a few principal components describe the
motions of the structures, and these usually relate to the functional dynamics. This dynamics
information provides strong evidence for the plasticity of protein and RNA structures, and also
suggests that these structures almost always have a highly limited repertoire of motions. In some
cases, such as many enzymes the dominant motions are opening and closing over the active site.
For myoglobin the changes are smalle, reflecting in part the small changes in sequence, but
nonetheless they show characteristic details in their motions that are species dependent.
We are computing pathways for transitions between different conformations, by generating
structures with a Metropolis Monte Carlo method, using free energies for structural intermediates
computed using our 4-body potentials and entropies from elastic network models. These provide
effective pathways that traverse the space of the experimental structures. In some other cases
transitions can be initiated by exothermic reactions, and these transitions can be effected by
application of forces at or near the reaction center. This work provides new tools that can be used
to understand the sets of available structures.
