85 research outputs found
Computational models for large-scale simulations of facilitated diffusion
The binding of site-specific transcription factors to their genomic target sites is a key step in gene regulation. While the genome is huge, transcription factors belong to the least abundant protein classes in the cell. It is therefore fascinating how short the time frame is that they require to home in on their target sites. The underlying search mechanism is called facilitated diffusion and assumes a combination of three-dimensional diffusion in the space around the DNA combined with one-dimensional random walk on it. In this review, we present the current understanding of the facilitated diffusion mechanism and identify questions that lack a clear or detailed answer. One way to investigate these questions is through stochastic simulation and, in this manuscript, we support the idea that such simulations are able to address them. Finally, we review which biological parameters need to be included in such computational models in order to obtain a detailed representation of the actual process. © 2012 The Royal Society of Chemistry
Physicochemical Properties of Ion Pairs of Biological Macromolecules
Ion pairs (also known as salt bridges) of electrostatically interacting cationic and anionic moieties are important for proteins and nucleic acids to perform their function. Although numerous three-dimensional structures show ion pairs at functionally important sites of biological macromolecules and their complexes, the physicochemical properties of the ion pairs are not well understood. Crystal structures typically show a single state for each ion pair. However, recent studies have revealed the dynamic nature of the ion pairs of the biological macromolecules. Biomolecular ion pairs undergo dynamic transitions between distinct states in which the charged moieties are either in direct contact or separated by water. This dynamic behavior is reasonable in light of the fundamental concepts that were established for small ions over the last century. In this review, we introduce the physicochemical concepts relevant to the ion pairs and provide an overview of the recent advancement in biophysical research on the ion pairs of biological macromolecules
Temperature Dependence of Internal Motions of Protein Side-Chain NH<sub>3</sub><sup>+</sup> Groups: Insight into Energy Barriers for Transient Breakage of Hydrogen Bonds
Although
charged side chains play important roles in protein function,
their dynamic properties are not well understood. Nuclear magnetic
resonance methods for investigating the dynamics of lysine side-chain
NH<sub>3</sub><sup>+</sup> groups were established recently. Using
this methodology, we have studied the temperature dependence of the
internal motions of the lysine side-chain NH<sub>3</sub><sup>+</sup> groups that form ion pairs with DNA phosphate groups in the HoxD9
homeodomain–DNA complex. For these NH<sub>3</sub><sup>+</sup> groups, we determined order parameters and correlation times for
bond rotations and reorientations at 15, 22, 28, and 35 °C. The
order parameters were found to be virtually constant in this temperature
range. In contrast, the bond-rotation correlation times of the NH<sub>3</sub><sup>+</sup> groups were found to depend strongly on temperature.
On the basis of transition state theory, the energy barriers for NH<sub>3</sub><sup>+</sup> rotations were analyzed and compared to those
for CH<sub>3</sub> rotations. Enthalpies of activation for NH<sub>3</sub><sup>+</sup> rotations were found to be significantly higher
than those for CH<sub>3</sub> rotations, which can be attributed to
the requirement of hydrogen bond breakage. However, entropies of activation
substantially reduce the overall free energies of activation for NH<sub>3</sub><sup>+</sup> rotations to a level comparable to those for
CH<sub>3</sub> rotations. This entropic reduction in energy barriers
may accelerate molecular processes requiring hydrogen bond breakage
and play a kinetically important role in protein function
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