An adaptive bin framework search method for a beta-sheet protein homopolymer model

In this work, we introduce a novel approach for solving this conformation search problem based on the use of a bin framework for adaptively storing and retrieving promising locally optimal solutions. Our approach provides a rich and general framework within which a broad range of adaptive or reactive search strategies can be realized. Here, we introduce adaptive mechanisms for choosing which conformations should be stored, based on the set of conformations already stored in memory, and for biasing choices when retrieving conformations from memory in order to overcome search stagnation.We show that our bin framework combined with a widely used optimization method, Monte Carlo search, achieves significantly better performance than state-of-the-art generalized ensemble methods for a well-known protein-like homopolymer model on the face-centered cubic lattice.Considering the close connection between the function of proteins and their three-dimensional (tertiary) structure, there are many reasons for studying protein folding; these include the desire to predict protein function based on sequence data (via tertiary structure prediction), to better understand a number of diseases that are directly caused by protein misfolding, aggregation and fibrillogenesis (some of which include Alzheimer's, Huntington's and prion disease as well as cystic fibrosis [1]), and to design proteins with desired structure and function. Since experimental methods (X-ray crystallography and NMR) for protein structure determination are highly labour intensive and require purification and, in the case of X-ray crystallography, crystallization of proteins, computational methods for predicting protein structure from sequence are very attractive.The ab initio protein folding problem is the problem of predicting the tertiary structure (the native state) of a protein from its amino acid sequence by minimizing a given energy function. Even for simple models that discretize conformations on a lattice (gr