Lando Dmitri Y, Teif Vladimir B
Institute of Bioorganic Chemistry, Belarus National Academy of Sciences, Kuprevich St. 5/2, 220141 Minsk, Belarus.
J Biomol Struct Dyn. 2002 Oct;20(2):215-22. doi: 10.1080/07391102.2002.10506837.
A theoretical method for computer modeling of DNA condensation caused by ligand binding is developed. In the method, starting (s) and condensed (c) states are characterized by different free energies for ligand free DNA (F(s) and F(c) respectively), ligand binding constants (K(s) and K(c)) and stoichiometry dependent parameters (c(sm) and c(cm) - maximum relative concentration of bound ligands (per base pair) for starting and condensed state respectively). The method allows computation of the dependence of the degree of condensation (the fraction of condensed DNA molecules) on ligand concentration. Calculations demonstrate that condensation transition occurs under an increase in ligand concentration if F(s) < F(c) (i.e. S(sc) = exp [- (F(c) - F(s)) / (RT)], the equilibrium constant of the s-c transition, is low (S(sc) << 1)) and K(s) < K(c). It was also found that condensation is followed by decondensation at high ligand concentration if the condensed DNA state provides the number of sites for ligand binding less than the starting state (c(sm) > c(cm)). A similar condensation-decondensation effect was found in recent experimental studies. We propose its simple explanation.
开发了一种用于计算机模拟配体结合导致DNA凝聚的理论方法。在该方法中，起始（s）态和凝聚（c）态的特征在于游离配体的DNA具有不同的自由能（分别为F(s)和F(c)）、配体结合常数（K(s)和K(c)）以及化学计量相关参数（c(sm)和c(cm)——分别为起始态和凝聚态结合配体的最大相对浓度（每碱基对））。该方法能够计算凝聚程度（凝聚DNA分子的比例）对配体浓度的依赖性。计算表明，如果F(s) < F(c)（即s-c转变的平衡常数S(sc) = exp [- (F(c) - F(s)) / (RT)]较低（S(sc) << 1））且K(s) < K(c)，则在配体浓度增加时会发生凝聚转变。还发现，如果凝聚的DNA状态提供的配体结合位点数量少于起始状态（c(sm) > c(cm)），则在高配体浓度下凝聚后会发生解凝聚。在最近的实验研究中也发现了类似的凝聚-解凝聚效应。我们提出了其简单解释。
