Tamjidul Hoque

Twin Removal in Genetic Algorithms for Protein Structure Prediction Using Low-Resolution Model

This paper presents the impact of twins and the measures for their removal from the population of genetic algorithm (GA) when applied to effective conformational searching. It is conclusively shown that a twin removal strategy for a GA provides considerably enhanced performance when investigating solutions to complex ab initio protein structure prediction (PSP) problems in low-resolution model. Without twin removal, GA crossover and mutation operations can become ineffectual as generations lose their ability to produce significant differences, which can lead to the solution stalling. The paper relaxes the definition of chromosomal twins in the removal strategy to not only encompass identical, but also highly correlated chromosomes within the GA population, with empirical results consistently exhibiting significant improvements solving PSP problems.

Extended HP Model for Protein Structure Prediction

This paper describes a detailed investigation of a lattice-based HP (hydrophobic-hydrophilic) model for ab initio protein structure prediction (PSP). The outcome of the simplified HP lattice model has high degeneracy, which could mislead the prediction. The HPNX model was proposed to address the degeneracy problem as well as to avoid the conformational deformity with the hydrophilic (P) residues. We have experimentally shown that it is necessary to further improve the existing HPNX model. We have found and solved the critical error of another existing YhHX model. By extracting the significant features from the YhHX for the HPNX model, we have proposed a novel hHPNX model. Hybrid Genetic Algorithm (HGA) has been used to compare the predictability of these models and hHPNX outperformed other models. We preferred 3D face-centered-cube (FCC) lattice configuration to have closest resemblance to the real folded 3D protein.

A Guided Genetic Algorithm for Protein Folding Prediction Using 3D Hydrophobic-Hydrophilic Model

In this paper, a Guided Genetic Algorithm (GGA) has been presented for protein folding prediction (PFP) using 3D Hydrophobic-Hydrophilic (HP) model. Effective strategies have been formulated utilizing the core formation of the globular protein, which provides the guideline for the Genetic Algorithm (GA) while predicting protein folding. Building blocks containing Hydrophobic (H) -Hydrophilic (P or Polar) covalent bond are utilized such a way that it helps form a core that maximizes the fitness. A series of operators are developed including Diagonal Move and Tilt Move to assist in implementing the building blocks in three-dimensional space. The GGA outperformed Ungers GA in 3D HP model. The overall strategy incorporates a swing function that provides a mechanism to enable the GGA to test more potential solutions and also prevent it from developing a schema that may cause it to become trapped in local minima. Further, it helps the guidelines remain non-rigid. GGA provides improved and robust performance for PFP.

A hybrid genetic algorithm for 2d FCC hydrophobic-hydrophilic lattice model to predict protein folding

This paper presents a Hybrid Genetic Algorithm (HGA) for the protein folding prediction (PFP) applications using the 2D face-centred-cube (FCC) Hydrophobic-Hydrophilic (HP) lattice model. This approach enhances the optimal core formation concept and develops effective and efficient strategies to implement generalized short pull moves to embed highly probable short motifs or building blocks and hence forms the hybridized GA for FCC model. Building blocks containing Hydrophobic (H) – Hydrophilic (P or Polar) covalent bonds are utilized such a way as to help form a core that maximizes the |fitness|. The HGA helps overcome the ineffective crossover and mutation operations that traditionally lead to the stuck condition, especially when the core becomes compact. PFP has been strategically translated into a multi-objective optimization problem and implemented using a swing function, with the HGA providing improved performance in the 2D FCC model compared with the Simple GA.

Genetic Algorithm in Ab Initio Protein Structure Prediction Using Low Resolution Model: A Review

Proteins are sequences of amino acids bound into a linear chain that adopt a specific folded three-dimensional (3D) shape. This specific folded shape enables proteins to perform specific tasks. The protein structure prediction (PSP) by ab initio or de novo approach is promising amongst various available computational methods and can help to unravel the important relationship between sequence and its corresponding structure. This article presents the ab initio protein structure prediction as a conformational search problem in low resolution model using genetic algorithm. As a review, the essence of twin removal, intelligence in coding, the development and application of domain specific heuristics garnered from the properties of the resulting model and the protein core formation concept discussed are all highly relevant in attempting to secure the best solution.

Improved prediction of accessible surface area results in efficient energy function application

An accurate prediction of real value accessible surface area (ASA) from protein sequence alone has wide application in the field of bioinformatics and computational biology. ASA has been helpful in understanding the 3-dimensional structure and function of a protein, acting as high impact feature in secondary structure prediction, disorder prediction, binding region identification and fold recognition applications. To enhance and support broad applications of ASA, we have made an attempt to improve the prediction accuracy of absolute accessible surface area by developing a new predictor paradigm, namely REGAd(3)p, for real value prediction through classical Exact Regression with Regularization and polynomial kernel of degree 3 which was further optimized using Genetic Algorithm. ASA assisting effective energy function, motivated us to enhance the accuracy of predicted ASA for better energy function application. Our ASA prediction paradigm was trained and tested using a new benchmark dataset, proposed in this work, consisting of 1001 and 298 protein chains, respectively. We achieved maximum Pearson Correlation Coefficient (PCC) of 0.76 and 1.45% improved PCC when compared with existing top performing predictor, SPINE-X, in ASA prediction on independent test set. Furthermore, we modeled the error between actual and predicted ASA in terms of energy and combined this energy linearly with the energy function 3DIGARS which resulted in an effective energy function, namely 3DIGARS2.0, outperforming all the state-of-the-art energy functions. Based on Rosetta and Tasser decoy-sets 3DIGARS2.0 resulted 80.78%, 73.77%, 141.24%, 16.52%, and 32.32% improvement over DFIRE, RWplus, dDFIRE, GOAP and 3DIGARS respectively.

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.

Genetic algorithm feature-based resampling for protein structure prediction

Proteins carry out the majority of functionality on a cellular level. Computational protein structure prediction (PSP) methods have been introduced to speed up the PSP process due to manual methods, like nuclear magnetic resonance (NMR) and x-ray crystallography (XC) taking numerous months even years to produce a predicted structure for a target protein. A lot of work in this area is focused on the type of search strategy to employ. Two popular methods in the literature are: Monte Carlo based algorithms and Genetic Algorithms. Genetic Algorithms (GA) have proven to be quite useful in the PSP field, as they allow for a generic search approach, which alleviates the need to redefine the search strategies for separate sequences. They also lend themselves well to feature-based resampling techniques. Feature-based resampling works by taking previously computed local minima and combining features from them to create new structures that are more uniformly low in free energy. In this work we present a feature-based resampling genetic algorithm to refine structures that are outputted by PSP software. Our results indicate that our approach performs well, and produced an average 9.5% root mean square deviation (RMSD) improvement and a 17.36% template modeling score (TM-Score) improvement.

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.

Generalized schemata theorem incorporating twin removal for protein structure prediction

The schemata theorem, on which the working of Genetic Algorithm (GA) is based in its current form, has a fallacious selection procedure and incomplete crossover operation. In this paper, generalization of the schemata theorem has been provided by correcting and removing these limitations. The analysis shows that similarity growth within GA population is inherent due to its stochastic nature. While the stochastic property helps in GAs convergence. The similarity growth is responsible for stalling and becomes more prevalent for hard optimization problem like protein structure prediction (PSP). While it is very essential that GA should explore the vast and complicated search landscape, in reality, it is often stuck in local minima. This paper shows that, removal of members of population having certain percentage of similarity would keep GA perform better, balancing and maintaining convergence property intact as well as avoids stalling.