De novo protein structure prediction from amino acid sequence is one of the most challenging problems in computational biology. As one of the extensively explored mathematical models for protein folding, Hydrophobic-Polar (HP) model enables thorough investigation of protein structure formation and evolution. Although HP model discretizes the conformational space and simplifies the folding energy function, it has been proven to be an NP-complete problem. In this paper, we propose a novel protein folding framework FoldingZero, self-folding a de novo protein 2D HP structure from scratch based on deep reinforcement learning. FoldingZero features the coupled approach of a two-head (policy and value heads) deep convolutional neural network (HPNet) and a regularized Upper Confidence Bounds for Trees (R-UCT). It is trained solely by a reinforcement learning algorithm, which improves HPNet and R-UCT iteratively through iterative policy optimization. Without any supervision and domain knowledge, FoldingZero not only achieves comparable results, but also learns the latent folding knowledge to stabilize the structure. Without exponential computation, FoldingZero shows promising potential to be adopted for real-world protein properties prediction.
Approximation algorithms offer rigorous mathematical tools and fold a protein structure within polynomial time. However, it may lead to a weak approximation ratio, resulting in a structure far from the optimal solution. Hart and Istrail proposed an approximation algorithm with ratio 3 8 of the optimal score for the 3D cubic lattice structure @cite_16 . An improved approximation algorithm with 2 5 performance guarantees was further developed by the same authors @cite_1 . For the 2D square lattice, an approximation algorithm @cite_7 can achieve the approximation ratio of 1 3.
@cite_16 @cite_1 @cite_7
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We consider the problem of protein folding in the HP model on the two-dimensional square lattice. This problem is combinatorially equivalent to folding a string of 0's and 1's so that the string forms a self-avoiding walk on the lattice and the number of adjacent pairs of 1's is maximized. We present a linear-time 1 3-approximation algorithm for this problem, improving on the previous best approximation factor of 1 4. The approximation guarantee of this algorithm is based on an upper bound presented by Hart and Istrail [6] and used in all previous papers that address this problem. We show that this upper bound cannot be used to obtain an approximation factor better than 1 2. Abstract In this paper we study the Steiner tree problem in graphs for the case when vertices as well as edges have weights associated with them. A greedy approximation algorithm based on “spider decompositions” was developed by Klein and Ravi for this problem. This algorithm provides a worst case approximation ratio of 2 ln k , where k is the number of terminals. However, the best known lower bound on the approximation ratio is (1− o (1)) ln k , assuming that NP ⊈ DTIME [ n O (log log n ) ], by a reduction from set cover. We show that for the unweighted case we can obtain an approximation factor of ln k . For the weighted case we develop a new decomposition theorem and generalize the notion of “spiders” to “branch-spiders” that are used to design a new algorithm with a worst case approximation factor of 1.5 ln k . We then generalize the method to yield an approximation factor of (1.35+ e ) ln k , for any constant e >0. These algorithms, although polynomial, are not very practical due to their high running time, since we need to repeatedly find many minimum weight matchings in each iteration. We also develop a simple greedy algorithm that is practical and has a worst case approximation factor of 1.6103 ln k . The techniques developed for this algorithm imply a method of approximating node weighted network design problems defined by 0–1 proper functions as well. These new ideas also lead to improved approximation guarantees for the problem of finding a minimum node weighted connected dominating set. The previous best approximation guarantee for this problem was 3 ln n by Guha and Khuller. By a direct application of the methods developed in this paper we are able to develop an algorithm with an approximation factor of (1.35+ e ) ln n for any fixed e >0. ABSTRACT This paper considers the protein energy minimization problem for lattice and off-lattice protein folding models that explicitly represent side chains. Lattice models of proteins have proven useful tools for reasoning about protein folding in unrestricted continuous space through analogy. This paper provides the first illustration of how rigorous algorithmic analyses of lattice models can lead to rigorous algorithmic analyses of off-lattice models. We consider two side chain models: a lattice model that generalizes the HP model (Dill, 1985) to explicitly represent side chains on the cubic lattice and a new off-lattice model, the HP Tangent Spheres Side Chain model (HP-TSSC), that generalizes this model further by representing the backbone and side chains of proteins with tangent spheres. We describe algorithms with mathematically guaranteed error bounds for both of these models. In particular, we describe a linear time performance guaranteed approximation algorithm for the HP side chain model that... We present an improved semidefinite programming based approximation algorithm for the MAX CUT problem in graphs of maximum degree at most 3. The approximation ratio of the new algorithm is at least 0.9326. This improves, and also somewhat simplifies, a result of Feige, Karpinski and Langberg. We also observe that results of Hopkins and Staton and of Bondy and Locke yield a simple combinatorial 4 5-approximation algorithm for the problem. Finally, we present a combinatorial 22 27-approximation algorithm for the MAX CUT problem for regular cubic graphs.