Adaptive conformational restraints for interactive model rebuilding in Cartesian and torsion space

Abstract

When building atomic models into weak and/or low-resolution density, a common strategy is to restrain its conformation to that of a higher-resolution model of the same or similar sequence. When doing so, it is important to avoid over-restraining to the reference model in the face of disagreement with the experimental data. The most common strategy for this is the use of "top-out" potentials. These act like simple harmonic restraints within a defined range, but gradually weaken when the deviation between the model and reference grows larger than a defined transition point. In each current implementation, the rate at which the potential flattens beyond the transition region follows a fixed form - although the form chosen varies between implementations. A restraint potential with a tuneable rate of flattening would provide greater flexibility to encode the confidence in any given restraint. Here we describe two new such potentials: a Cartesian distance restraint derived from a recent generalisation of common loss functions, and a periodic torsion restraint based on a renormalisation of the von Mises distribution. Further, we describe their implementation as user-adjustable/switchable restraints in ISOLDE, and demonstrate their use in some real-world examples. SynopsisNew forms of adaptive or top-out distance and torsion restraints are described, suitable for restraining a model to match a reference structure during interactive rebuilding. In addition, their implementation in ISOLDE is described along with some illustrative example applications.