Optimal Length of Conformational Transition Region in Protein Search for Targets on DNA

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American Chemical Society

The starting point of many fundamental biological processes is associated with protein molecules finding and recognizing specific sites on DNA. However, despite a large number of experimental and theoretical studies on protein search for targets on DNA, many molecular aspects of underlying mechanisms are still not well understood. Experiments show that proteins bound to DNA can switch between slow recognition and fast search conformations. However, from a theoretical point of view, such conformational transitions should slow down the protein search for specific sites on DNA, in contrast to available experimental observations. In addition, experiments indicate that the nucleotide composition near the target site is more symmetrically homogeneous, leading to stronger effective interactions between proteins and DNA at these locations. However, as has been shown theoretically, this should also make the search less efficient, which is not observed. We propose a possible resolution of these problems by suggesting that conformational transitions occur only within a segment around the target where stronger interactions between proteins and DNA are observed. Two theoretical methods, based on continuum and discrete-state stochastic calculations, are developed, allowing us to obtain a comprehensive dynamic description for the protein search process in this system. The existence of an optimal length of the conformational transition zone with the shortest mean search time is predicted.

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Kochugaeva, Maria P., Berezhkovskii, Alexander M. and Kolomeisky, Anatoly B.. "Optimal Length of Conformational Transition Region in Protein Search for Targets on DNA." The Journal of Physical Chemistry Letters, 8, no. 17 (2017) American Chemical Society: 4049-4054. https://doi.org/10.1021/acs.jpclett.7b01750.

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