Search

The thermodynamic stability of a folded RNA is intricately tied to the counterions and the free energy of this interaction must be accounted for in any realistic RNA simulations. Extending a tight-binding model published previously, in this paper we investigate the fundamental structure of charges arising from the interaction between small functional RNA molecules and divalent ions such as Mg2+ that are especially conducive to stabilizing folded conformations. The characteristic nature of these charges is utilized to construct a discretely connected energy landscape that is then traversed via a novel application of a deterministic graph search technique. This search method can be incorporated into larger simulations of small RNA molecules and provides a fast and accurate way to calculate the free energy arising from the interactions between an RNA and divalent counterions. The utility of this algorithm is demonstrated within a fully atomistic Monte Carlo simulation of the P4-P6 domain of the Tetrahymena group I intron, in which it is shown that the counterionmediated free energy conclusively directs folding into a compact structure. [ABSTRACT FROM AUTHOR]

Using computer simulations to model the folding of proteins into their native states is computationally expensive due to the extraordinarily low degeneracy of the ground state. In this paper, we develop an efficient way to sample these folded conformations using Wang Landau sampling coupled with the configurational bias method (which uses an unphysical 'temperature' that lies between the collapse and folding transition temperatures of the protein). This method speeds up the folding process by roughly an order of magnitude over existing algorithms for the sequences studied. We apply this method to study the adsorption of intrinsically disordered hydrophobic polar protein fragments on a hydrophobic surface. We find that these fragments, which are unstructured in the bulk, acquire secondary structure upon adsorption onto a strong hydrophobic surface. Apparently, the presence of a hydrophobic surface allows these random coil fragments to fold by providing hydrophobic contacts that were lost in protein fragmentation. [ABSTRACT FROM AUTHOR]