"Biological cells are highly crowded due to the presence of various macromolecules. Here, the macromolecular crowding effects on DNA structure were investigated via computer simulations. Molecular dynamics simulations of DNA with crowder proteins showed that B-form of DNA is stabilized resulting from non-specific interactions of crowder proteins with DNA sugar-phosphate backbone, while the reduced dielectric response of cellular environments was found to favor Alike conformations as shown by implicit solvent simulations of DNA in reduced dielectric environments. Overall, the results obtained here suggest that different aspects of cellular crowding have opposite impacts on DNA structure. As the largest molecule in the cell, genomic DNA also occupies a large fraction of the bacterial cell and causes crowding. An experimentally-driven multiscale modeling protocol was developed to study the three-dimensional structure of bacterial chromosomes and their effects on protein diffusion. Using this protocol, three dimensional structures of Caulobacter crescentus chromosome at base-pair resolution were generated. Investigation of these models provided insights into chromosome structural variability and organization. Coarse-grained Brownian dynamics simulations of these chromosome models in the presence of proteins, on the other hand, suggest that protein diffusion becomes slower and anomalous when around DNA."--Page 56 [ii].
Read
