A Theoretician’s Adventures in DNA Land

Nucleic acids, exemplified by the molecule of life, DNA, are giant molecules with fascinating properties. This talk will illustrate how molecular modeling helps one to understand the nucleic acid properties at different spatial and temporal scales and lead to designs for molecular electronics and molecular assembly. First, it will be shown how a combination of molecular dynamics and quantum mechanical calculations reveals the effect of thermal fluctuations on molecular conductance in peptide nucleic acid (PNA). It turns out that the increased amount of fluctuations leads to a boost in PNA conductance, in agreement with experiment. Next, steered molecular dynamics simulations will demonstrate that a mechanical stress causes DNA to adapt a completely new structural form, the so-called zip-DNA. The zip-DNA overturns a well-established principle of DNA structure, resolves a long-standing contradiction in the field, and is predicted to possess a larger conductivity than the classic B-DNA. Finally, a combination of elastic rod DNA modeling with molecular dynamics simulations will shed light on the mechanism of the lac repressor, a celebrated genome regulator protein of E. Coli. The simulations reveal how a combination of the headgroup mobility with a structural locking mechanism allows the repressor to keep the lac operon DNA in the looped state, shutting down the synthesis of unneeded protein. At the end of the talk, perspectives for molecular modeling and nucleic acid-based molecular design will be discussed.