On the role of London dispersion forces in biomolecular structure determination.

A DNA dodecamer and the methyladenine···methylthymine (mA···mT) complex in aqueous environment have been studied by means of molecular dynamics simulation, with a modified force field accounting for the hypothetical absence of London dispersion forces. Under these conditions, the mA···mT complex is preserved, while the double-helical DNA oligomer passes via an extended, ladder-like intermediate to a collapsed structure. The results are interpreted in terms of stability and specificity of the structure of studied complexes. While the hydrophobic effect of the solvent accounts for the sufficient stabilization of the complex, the appearance of the native biomolecular conformation is attributed to the London dispersion forces. Thus, the London dispersion seems to provide the native structure of a biomolecular complex with the largest additional stabilization, preferring it among several (or many) possible aggregated structures. The observations are affected by the construction of the modified force field, and this effect is discussed thoroughly. The fundamental issues are the coupling of the components of the Lennard-Jones potential and the way to separate them. Based on the observations, the description of nonbonded interactions with the current biomolecular force fields is discussed. It is proposed that a novel force field composed of physically correct components to describe nonbonded interactions could exhibit more favorable performance in certain up-to-date applications.