Abstract

The projection of molecular processes onto a small set of relevant descriptors, the so-called reaction coordinates or collective variables (CVs), is a technique nowadays routinely employed by the biomolecular simulation community. In this work, we implemented two CVs to manipulate the orientation (i.e., angle) ((mu) over right arrow (a)) and magnitude (vertical bar(mu) over right arrow vertical bar) of the electric dipole moment. In doing so, we studied the thermodynamics of water orientation under the application of external voltages and the folding of two polypeptides at zero-field conditions. The projection of the free-energy [potential of mean force (PMF)] along water orientation defined an upper limit of around 0.3 V for irrelevant thermodynamic effects. On the other hand, sufficiently strong (mu) over right arrow (a) restraints applied on 12-alanine (Ala(12)) triggered structural effects because of the alignment of local dipoles; for lower restraints, a full-body rotation is achieved. The manipulation of vertical bar(mu) over right arrow vertical bar produced strong perturbations on the secondary structure of Ala(12), promoting an enhanced sampling to its configurational space. Rigorous free-energy calculations in the form of 2-D PMFs for deca-alanine showed the utility of vertical bar(mu) over right arrow vertical bar as a reaction coordinate to study folding in small alpha helices. As a whole, we propose that the manipulation of both components of the dipole moment, (mu) over right arrow (a) and vertical bar(mu) over right arrow vertical bar, provides thermodynamics insights into the structural conformation and stability of biomolecules. These new CVs are implemented in the Colvars module, available for NAMD and LAMMPS.