Influence of strongly stabilized sites on DNA melting: A comparison of theory with experiment

Abstract

Strong local stabilization of the double helix can be an alternative to the interstrand crosslinks formed in DNA by some antitumor drugs. Therefore, we have carried out a computer modeling of the thermodynamic properties of DNA that contains strongly stabilized sites (SSSs). Melting of DNA locally fastened by SSSs was compared with DNA that includes interstrand crosslinks. Using experimental data from the literature and the results of our calculations, we have shown that SSSs really exist: some irreversibly bound protein molecules and chemical modifications caused by some ruthenium and antitumor platinum compounds form such sites in DNA. The theoretical calculated results for the increase of melting temperatures for random distribution of SSSs are consistent with experimental data.

Temporal behavior of DNA thermal stability in the presence of platinum compounds. Role of monofunctional and bifunctional adducts

“…At the r = 0.05 value used in this study, their per nucleotide number is 0.003 and 0.006. As follows from our recent calculations [49,66,77], interstrand crosslinks of the relative concentration 0.003 increase melting temperature of long DNA by 1.3°C if they do not cause distortions at sites of their location and by 1.6°C in the case of strong local stabilization. This corresponds to approximately 10% of the total change in δT m caused by all final modifications of cisplatin in alkaline medium (~12°C, Fig.…”

“…Besides a local change in DNA structure and thermal stability that is generated by all types of chemical modifications, interstrand crosslinks increase the thermal stability of short DNAs prohibiting strand dissociation [39,40,62,63]. Additional stabilization of long DNAs is caused by formation of additional loops in melted regions [73][74][75][76][77][78]. The fraction of interstrand crosslinks accounts for 6% and 12% for cisplatin and transplatin, respectively [10][11][12].…”

Eigen Model with Correlated Multiple Mutations and Solution of Error Catastrophe Paradox in the Origin of Life

“…In recent decades, ideas and methods of physics have been widely used to study biological problems at the molecular level, e.g., the structure and folding of proteins, [1][2][3][4] structure and thermal properties of DNA and RNA, [5][6][7][8] molecular models of biological evolution and the origin of life, [9][10][11][12][13][14][15][16][17][18][19][20][21] etc. In this paper, we will address an interesting problem related to the origin of life.…”

Universal geometrical factor of protein conformations as a consequence of energy minimization

“…In recent decades, physical methods have been widely used to study properties and structures of biopolymers [1][2][3], including DNA [4,5], RNA [6], and protein [7][8][9][10]. Proteins assume specified conformations from their chemical compositions or sequences to develop biological activity and functional specificity.…”