RT Journal Article
SR Electronic
T1 A multiscale analysis of DNA phase separation: From atomistic to mesoscale level
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 375626
DO 10.1101/375626
A1 Tiedong Sun
A1 Alexander Mirzoev
A1 Vishal Minhas
A1 Nikolay Korolev
A1 Alexander P. Lyubartsev
A1 Lars Nordenskiöld
YR 2019
UL http://biorxiv.org/content/early/2019/05/02/375626.abstract
AB DNA condensation and phase separation is of utmost importance for DNA packing in vivo with important applications in medicine, biotechnology and polymer physics. The presence of hexagonally ordered DNA is observed in virus capsids, sperm heads and in dinoflagellates. Rigorous modelling of this process in all-atom MD simulations is presently difficult to achieve due to size and time scale limitations. We used a hierarchical approach for systematic multiscale coarse-grained (CG) simulations of DNA phase separation induced by the three-valent cobalt(III)-hexammine (CoHex3+). Solvent-mediated effective potentials for a CG model of DNA were extracted from all-atom MD simulations. Simulations of several hundred 100-bp-long CG DNA oligonucleotides in the presence of explicit CoHex3+ ions demonstrated aggregation to a liquid crystalline hexagonally ordered phase. Following further coarse-graining and extraction of effective potentials, we conducted modelling at mesoscale level. In agreement with electron microscopy observations, simulations of an 10.2-kbp-long DNA molecule showed phase separation to either a toroid or a fibre with distinct hexagonal DNA packing. The mechanism of toroid formation is analysed in detail. The approach used here is based only on the underlying all-atom force field and uses no adjustable parameters and may be generalized to modelling chromatin up to chromosome size.