Effect of osmolytes of different type on DNA behavior in aqueous solution. Experimental and theoretical studies

Abstract Osmolytes, the small organic molecules accumulated in cells under environmental stress, can modulate the stability of biopolymers such as proteins and DNA. In spite of many years of research, there is no established molecular mechanism of the influence of osmolytes on DNA structure. Here, we used two model osmolytes that denature (urea) or stabilize (trimethylglycine, TMG) proteins to study their effect on DNA in aqueous solutions using a combination of spectroscopic, calorimetric and simulation methods. We found that both urea and TMG dehydrate DNA and shift the conformational equilibrium from B- to A-DNA form, despite different solvation properties. The isolated vibrational spectra of osmolytes and analysis of preferential accumulation indicate a lack of direct specific interaction with DNA in ternary solutions. Besides the influence of TMG and urea on DNA hydration, we studied and analyzed the orientational and spatial distribution of osmolytes around DNA. Analysis of hydrogen bonds and theoretical calculations of interactions with native and denatured DNA show strong negative interactions with bases of dissociated DNA: while TMG preferentially interacts with guanine, urea interacts equally strongly with all bases. This high affinity of both TMG and urea towards DNA bases appears to be the cause of their denaturing properties.