Deconstructing the energy landscape: Constraint-based algorithms for folding heteropolymers

Abstract

We apply the computational methodology of phase retrieval to the problem of folding heteropolymers. The ground state fold of the polymer is defined by the intersection of two sets in the configuration space of its constituent monomers: a geometrical chain constraint and a threshold constraint on the contact energy. A dynamical system is then defined in terms of the projections to these constraint sets, such that its fixed points solve the set intersection problem. We present results for two off-lattice hydrophobic-polar models: one with only rotameric degrees of freedom, and one proposed by Stillinger et al. [Phys. Rev. E 48, 1469 (1993)] with flexible bond angles. Our phase retrieval inspired algorithm is competitive with more established algorithms and even finds lower-energy folds for one of the longer polymer chains.