  Recent advances in distance-based protein folding have led to a paradigm
shift in protein structure prediction. Through sufficiently precise estimation
of the inter-residue distance matrix for a protein sequence, it is now feasible
to predict the correct folds for new proteins much more accurately than ever
before. Despite the exciting progress, a dedicated visualization system that
can dynamically capture the distance-based folding process is still lacking.
Most molecular visualizers typically provide only a static view of a folded
protein conformation, but do not capture the folding process. Even among the
selected few graphical interfaces that do adopt a dynamic perspective, none of
them are distance-based. Here we present PolyFold, an interactive visual
simulator for dynamically capturing the distance-based protein folding process
through real-time rendering of a distance matrix and its compatible spatial
conformation as it folds in an intuitive and easy-to-use interface. PolyFold
integrates highly convergent stochastic optimization algorithms with on-demand
customizations and interactive manipulations to maximally satisfy the geometric
constraints imposed by a distance matrix. PolyFold is capable of simulating the
complex process of protein folding even on modest personal computers, thus
making it accessible to the general public for fostering citizen science. Open
source code of PolyFold is freely available for download at
https://github.com/Bhattacharya-Lab/PolyFold. It is implemented in
cross-platform Java and binary executables are available for macOS, Linux, and
Windows.
