M. A. Hakim Newton

A new genetic algorithm for simplified protein structure prediction

In this paper, we present a new genetic algorithm for protein structure prediction problem using face-centred cubic lattice and hydrophobic-polar energy model. Our algorithm uses i) an exhaustive generation approach to diversify the search; ii) a novel hydrophobic core-directed macro move to intensify the search; and iii) a random-walk strategy to recover from stagnation. On a set of standard benchmark proteins, our algorithm significantly outperforms the state-of-the-art algorithms for the same models.

Kangaroo: an efficient constraint-based local search system using lazy propagation

In this paper, we introduce Kangaroo, a constraint-based local search system. While existing systems such as Comet maintain invariants after every move, Kangaroo adopts a lazy strategy, updating invariants only when they are needed. Our empirical evaluation shows that Kangaroo consistently has a smaller memory footprint than Comet, and is usually significantly faster.

Memory-based local search for simplified protein structure prediction

Protein structure prediction is one of the most challenging problems in computational biology. Given a proteins amino acid sequence, a simplified version of the problem is to find an on-lattice self-avoiding walk that minimizes the interaction energy among the amino acids. In this paper, we present a memory-based local search method for the simplified problem using Hydrophobic-Polar energy model and Face Centered Cubic lattice. By memorizing local minima and then avoiding their neighbohood, our approach significantly improves the state-of-the-art local search method for protein structure prediction on a set of standard benchmark proteins.

The road not taken: retreat and diverge in local search for simplified protein structure prediction

BackgroundGiven a proteins amino acid sequence, the protein structure prediction problem is to find a three dimensional structure that has the native energy level. For many decades, it has been one of the most challenging problems in computational biology. A simplified version of the problem is to find an on-lattice self-avoiding walk that minimizes the interaction energy among the amino acids. Local search methods have been preferably used in solving the protein structure prediction problem for their efficiency in finding very good solutions quickly. However, they suffer mainly from two problems: re-visitation and stagnancy.ResultsIn this paper, we present an efficient local search algorithm that deals with these two problems. During search, we select the best candidate at each iteration, but store the unexplored second best candidates in a set of elite conformations, and explore them whenever the search faces stagnation. Moreover, we propose a new non-isomorphic encoding for the protein conformations to store the conformations and to check similarity when applied with a memory based search. This new encoding helps eliminate conformations that are equivalent under rotation and translation, and thus results in better prevention of re-visitation.ConclusionOn standard benchmark proteins, our algorithm significantly outperforms the state-of-the art approaches for Hydrophobic-Polar energy models and Face Centered Cubic Lattice.

Spiral search: a hydrophobic-core directed local search for simplified PSP on 3D FCC lattice

BackgroundProtein structure prediction is an important but unsolved problem in biological science. Predicted structures vary much with energy functions and structure-mapping spaces. In our simplified ab initio protein structure prediction methods, we use hydrophobic-polar (HP) energy model for structure evaluation, and 3-dimensional face-centred-cubic lattice for structure mapping. For HP energy model, developing a compact hydrophobic-core (H-core) is essential for the progress of the search. The H-core helps find a stable structure with the lowest possible free energy.ResultsIn order to build H-cores, we present a new Spiral Search algorithm based on tabu-guided local search. Our algorithm uses a novel H-core directed guidance heuristic that squeezes the structure around a dynamic hydrophobic-core centre. We applied random walks to break premature H-cores and thus to avoid early convergence. We also used a novel relay-restart technique to handle stagnation.ConclusionsWe have tested our algorithms on a set of benchmark protein sequences. The experimental results show that our spiral search algorithm outperforms the state-of-the-art local search algorithms for simplified protein structure prediction. We also experimentally show the effectiveness of the relay-restart.

An efficient encoding for simplified protein structure prediction using genetic algorithms

Protein structure prediction is one of the most challenging problems in computational biology and remains unsolved for many decades. In a simplified version of the problem, the task is to find a self-avoiding walk with the minimum free energy assuming a discrete lattice and a given energy matrix. Genetic algorithms currently produce the state-of-the-art results for simplified protein structure prediction. However, performance of the genetic algorithms largely depends on the encodings they use in representing protein structures and the twin removal technique they use in eliminating duplicate solutions from the current population. In this paper, we present a new efficient encoding for protein structures. Our encoding is nonisomorphic in nature and results into efficient twin removal. This helps the search algorithm diversify and explore a larger area of the search space. In addition to this, we also propose an approximate matching scheme for removing near-similar solutions from the population. Our encoding algorithm is generic and applicable to any lattice type. On the standard benchmark proteins, our techniques significantly improve the state-of-the-art genetic algorithm for hydrophobic-polar (HP) energy model on face-centered-cubic (FCC) lattice.

Random-walk: a stagnation recovery technique for simplified protein structure prediction

Protein structure prediction is a challenging optimisation problem to the computer scientists. A large number of existing (meta-)heuristic search algorithms attempt to solve the problem by exploring possible structures and finding the one with minimum free energy. However, these algorithms often get stuck in local minima and thus perform poorly on large sized proteins. In this paper, we present a random-walk based stagnation recovery approach. We tested our approach on tabu-based local search as well as population based genetic algorithms. The experimental results show that, random-walk is very effective for escaping from local minima for protein structure prediction on face-centred-cubic lattice and hydrophobic-polar energy model.

Mixing energy models in genetic algorithms for on-lattice protein structure prediction.

Protein structure prediction (PSP) is computationally a very challenging problem. The challenge largely comes from the fact that the energy function that needs to be minimised in order to obtain the native structure of a given protein is not clearly known. A high resolution 20 × 20 energy model could better capture the behaviour of the actual energy function than a low resolution energy model such as hydrophobic polar. However, the fine grained details of the high resolution interaction energy matrix are often not very informative for guiding the search. In contrast, a low resolution energy model could effectively bias the search towards certain promising directions. In this paper, we develop a genetic algorithm that mainly uses a high resolution energy model for protein structure evaluation but uses a low resolution HP energy model in focussing the search towards exploring structures that have hydrophobic cores. We experimentally show that this mixing of energy models leads to significant lower energy structures compared to the state-of-the-art results.

How Good Are Simplified Models for Protein Structure Prediction

Protein structure prediction (PSP) has been one of the most challenging problems in computational biology for several decades. The challenge is largely due to the complexity of the all-atomic details and the unknown nature of the energy function. Researchers have therefore used simplified energy models that consider interaction potentials only between the amino acid monomers in contact on discrete lattices. The restricted nature of the lattices and the energy models poses a twofold concern regarding the assessment of the models. Can a native or a very close structure be obtained when structures are mapped to lattices? Can the contact based energy models on discrete lattices guide the search towards the native structures? In this paper, we use the protein chain lattice fitting (PCLF) problem to address the first concern; we developed a constraint-based local search algorithm for the PCLF problem for cubic and face-centered cubic lattices and found very close lattice fits for the native structures. For the second concern, we use a number of techniques to sample the conformation space and find correlations between energy functions and root mean square deviation (RMSD) distance of the lattice-based structures with the native structures. Our analysis reveals weakness of several contact based energy models used that are popular in PSP.

A local search embedded genetic algorithm for simplified protein structure prediction

No single algorithm suits the best for the protein structure prediction problem. Therefore, researchers have tried hybrid techniques to mix the power of different strategies to gain improvements. In this paper, we present a hybrid search framework that embeds a tabu-based local search within a population based genetic algorithm. We applied our hybrid algorithm on simplified protein structure prediction problem. We use a low-resolution ab initio search method with the hydrophobic-polar energy model and face-centred-cubic lattice. Within the genetic algorithm, we apply local search in two different situations: i) only once at the beginning and ii) every time at search stagnation. At the beginning, we apply local search to improve the randomly generated individuals and use them as an initial population for the genetic algorithm. Later, we apply local search after applying a random-walk at situations where the genetic algorithm gets stuck. In both cases, the use of local search is to improve the randomised solutions quickly. We experimentally show that our hybrid approach outperforms the state-of-the-art approaches.