Molecular modeling as a visualization tool in design of DNA crosslinked polyacrylamide

Polymers such as polyacrylamide form a diverse class of biomaterials in use today. The experimental research performed by our group has demonstrated how a critical concentration of crosslinking DNA strands can lead to gel formation in the polyacrylamide. The removal or addition of DNA strands can reverse or significantly increase the stiffness and strength of the gel. DNA is a versatile material for the exploration of nanoscale structures because its hybridization chemistry is very specific. DNA crosslinked gels use end-modified DNA oligonucleotides in the gels. The ability to choose the base sequence in the DNA crosslinks offers an opportunity to engineer the nanoscale structure of this material. However, it is extremely difficult to visualize the sequence of events that occurs when DNA is crosslinked with polyacrylamide. Computer modeling is a tool that enables the researchers to study the structural aspects of the newly engineered DNA crosslinkers. In this study, polyacrylamide gel crosslinked with DNA has been assayed with respect to energy and size using AMBER 7.0 software [1]. Since DNA-crosslinked gels are likely to find a range of applications it is important to know how to tailor the gel composition for a particular application. It is also of interest to know what the composition is that would induce the greatest change in stiffness. The molecular models generated in AMBER survey the mechanical properties of the gel as a function of crosslinker density, polyacrylamide density, and crosslinker length. The structure of an equilibrium state is computed using an explicitly solvated model. Visual inspection of the model determines other mechanical properties of the gel and helps predict chemical interactions. A long-term goal of this work is to use computer assisted modeling techniques to guide the experiments, to predict linker stiffness, and to examine other mechanical properties of the DNA crosslinker.