MELTING OF CROSS-LINKED DNA - III - CALCULATION OF DIFFERENTIAL MELTING CURVES

In our previous papers I and II (D. Y. Lando et al, J. Biomol. Struct. Dynam. (1997) v. 15, N1, p.129-140, p. 141-150), two methods were dev eloped for calculation of melting curves of cross-linked DNA. One of t hem is based on Poland's and another on the Fixman-Freire approach. In the present communication, III, a new theoretical method is developed for computation of differential melting curves of DNAs cross-linked b y anticancer drugs and their inactive analogs. As Poland's approach, t he method allows study of the influence of the loop entropy factor, de lta(n), on melting behavior (n is the length of a loop in base pairs). However the method is much faster and requires computer time that inh erent for the most rapid Fixman-Freire calculation approach. In contra st to the computation procedures described before in communications I and II, the method is suitable for computation of differential melting curves in the case of long DNA chains, arbitrary loop entropy factors of melted regions and arbitrary degree of cross-linking including ver y low values that occur in vivo after administration of antitumor drug s. The method is also appropriate for DNAs without cross-links. The re sults of calculation demonstrate that even very low degree of cross-li nking alters the DNA differential melting curve. Cross-linking also ma rkedly strengthens the influence of particular function delta(n) upon melting behavior.