MOLECULAR-DYNAMICS SIMULATIONS OF SMALL DNA PLASMIDS - EFFECTS OF SEQUENCE AND SUPERCOILING ON INTRAMOLECULAR MOTIONS

Small (600 base pair) DNA plasmids were modeled with a simplified repr esentation (3DNA) and the intramolecular motions were studied using mo lecular mechanics and molecular dynamics techniques. The model is deta iled enough to incorporate sequence effects. At the same time, it is s imple enough to allow long molecular dynamics simulations. The simulat ions revealed that large-scale slithering occurs in a homogeneous sequ ence. In a heterogeneous sequence, containing numerous small intrinsic curves, the centers of the curves are preferentially positioned at th e tips of loops. With more curves than loop tips (two in unbranched su percoiled DNA), the heterogeneous sequence plasmid slithers short dist ances to reposition other curves into the loop tips. However, the DNA is immobilized most of the time, with the loop tips positioned over a few favored curve centers. Branching or looping also appears in the he terogeneous sequence as a new method of repositioning the loop tips. I nstead of a smooth progression of increasing writhing with increasing linking difference, theoretical studies have predicted that there is a threshold between unwrithed and writhed DNA at a linking difference b etween one and two. This has previously been observed in simulations o f static structures and is demonstrated here for dynamic homogeneous c losed DNA. Such an abrupt transition is not found in the heterogeneous sequence in both the static and dynamic cases. (C) 1996 John Wiley & Sons, Inc.