Modelling the biomechanical properties of DNA using computer simulation

Duplex DNA must remain stable when not in use to protect the genetic material. However, the two strands must be separated whenever genes are copied or expressed to expose the coding strand for synthesis of complementary RNA or DNA bases. Therefore, the double stranded structure must be relatively easy to take apart when required. These conflicting biological requirements have important implications for the mechanical properties of duplex DNA. Considerable insight into the forces required to denature DNA has been provided by nanomanipulation experiments, which measure the mechanical properties of single molecules in the laboratory. This paper describes recent computer simulation methods that have been developed to mimic nanomanipulation experiments and which, quite literally, ‘destruction test’ duplex DNA in silico. The method is verified by comparison with single molecule stretching experiments that measure the force required to unbind the two DNA strands. The model is then extended to investigate the thermodynamics of DNA bending and twisting. This is of biological importance as the DNA must be very tightly packaged to fit within the nucleus, and is therefore usually found in a highly twisted or supercoiled state (in bacteria) or wrapped tightly around histone proteins into a densely compacted structure (in animals). In particular, these simulations highlight the importance of thermal fluctuations and entropy in determining the biomechanical properties of DNA. This has implications for the action of DNA processing molecular motors, and also for nanotechnology. Biological machines are able to manipulate single molecules reliably on an energy scale comparable to that of thermal noise. The hope is that understanding the statistical mechanisms that a cell uses to achieve this will be invaluable for the future design of ‘nanoengines’ engineered to perform new technological functions at the nanoscale.