A local average distance descriptor for flexible protein structure comparison

Wang, Hsin-Wei; Chu, Chia-Han; Wang, Wen-Ching; Pai, Tun-Wen

doi:10.1186/1471-2105-15-95

Cited by 7 publications

(2 citation statements)

References 66 publications

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“…There are several recent studies on new methods for analyzing conformational sampling and dynamics of proteins via MD simulations which imply the importance of this field (46)(47)(48)(49)(50)(51)(52)(53), however, there is long pace remains to the attainment of the perfection (54).…”

Section: Discussionmentioning

confidence: 99%

Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study

2016

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Protein flexibility probably is a phenomenon that can make the existence of the many protein conformations possible in contrast to a limited number. Many conformations in a protein are needed for doing many functions. For instance, based on searching IntAct PPI database with the UniprotKB accession number of hCDK2: P24941, hCDK2 has at least 200 different interactions with other proteins in addition to interactions by itself (1). As a structural characteristic, protein flexibility plays many functional roles with respect to different aspects of the proteins as well. Examples in this regard are enzyme catalysis and ligand-receptor interactions, substrate and ligand orientation, the turnover rate of the substrates, and reduction of the free energy barrier in the active sites (2).In structural bioinformatics tools, there are many instances regarding protein flexibility applications and usefulness; as an example, improvement of the small ligand-receptor docking (3,4 Background: Protein flexibility, which has been referred as a dynamic behavior has various roles in proteins' functions. Furthermore, for some developed tools in bioinformatics, such as protein-protein docking software, considering the protein flexibility, causes a higher degree of accuracy. Through undertaking the present work, we have accomplished the quantification plus analysis of the variations in the human Cyclin Dependent Kinase 2 (hCDK2) protein flexibility without affecting a significant change in its initial environment or the protein per se. Objectives:The main goal of the present research was to calculate variations in the flexibility for each residue of the hCDK2, analysis of their flexibility variations through clustering, and to investigate the functional aspects of the residues with high flexibility variations. Materials and Methods: Using Gromacs package (version 4.5.4), three independent molecular dynamics (MD) simulations of the hCDK2 protein (PDB ID: 1HCL) was accomplished with no significant changes in their initial environments, structures, or conformations, followed by Root Mean Square Fluctuations (RMSF) calculation of these MD trajectories. The amount of variations in these three curves of RMSF was calculated using two formulas.Results: More than 50% of the variation in the flexibility (the distance between the maximum and the minimum amount of the RMSF) was found at the region of Val-154. As well, there are other major flexibility fluctuations in other residues. These residues were mostly positioned in the vicinity of the functional residues. The subsequent works were done, as followed by clustering all hCDK2 residues into four groups considering the amount of their variability with respect to flexibility and their position in the RMSF curves. Conclusions:This work has introduced a new class of flexibility aspect of the proteins' residues. It could also help designing and engineering proteins, with introducing a new dynamic aspect of hCDK2, and accordingly, for the other similar globular proteins. In addition, it could provide a...

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Section: Discussionmentioning

confidence: 99%

Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study

2016

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“…Polypeptides consist of a maximum of 20 amino acids. The function of a given protein is determined by the native structure or its polymer structure, which correlates with particular protein functions [ 1 ]. The native three-dimensional structure of a protein primarily depends on its amino acid sequence [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Protein folding prediction in the HP model using ions motion optimization with a greedy algorithm

Yang

Lin

et al. 2018

BioData Mining

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BackgroundThe function of a protein is determined by its native protein structure. Among many protein prediction methods, the Hydrophobic-Polar (HP) model, an ab initio method, simplifies the protein folding prediction process in order to reduce the prediction complexity.ResultsIn this study, the ions motion optimization (IMO) algorithm was combined with the greedy algorithm (namely IMOG) and implemented to the HP model for the protein folding prediction based on the 2D-triangular-lattice model. Prediction results showed that the integration method IMOG provided a better prediction efficiency in a HP model. Compared to others, our proposed method turned out as superior in its prediction ability and resilience for most of the test sequences. The efficiency of the proposed method was verified by the prediction results. The global search capability and the ability to escape from the local best solution of IMO combined with a local search (greedy algorithm) to the new algorithm IMOG greatly improve the search for the best solution with reliable protein folding prediction.ConclusionOverall, the HP model integrated with IMO and a greedy algorithm as IMOG provides an improved way of protein structure prediction of high stability, high efficiency, and outstanding performance.

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Using Variable-Length Aligned Fragment Pairs and an Improved Transition Function for Flexible Protein Structure Alignment

Cao

2017

Journal of Computational Biology

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With the rapid growth of known protein 3D structures in number, how to efficiently compare protein structures becomes an essential and challenging problem in computational structural biology. At present, many protein structure alignment methods have been developed. Among all these methods, flexible structure alignment methods are shown to be superior to rigid structure alignment methods in identifying structure similarities between proteins, which have gone through conformational changes. It is also found that the methods based on aligned fragment pairs (AFPs) have a special advantage over other approaches in balancing global structure similarities and local structure similarities. Accordingly, we propose a new flexible protein structure alignment method based on variable-length AFPs. Compared with other methods, the proposed method possesses three main advantages. First, it is based on variable-length AFPs. The length of each AFP is separately determined to maximally represent a local similar structure fragment, which reduces the number of AFPs. Second, it uses local coordinate systems, which simplify the computation at each step of the expansion of AFPs during the AFP identification. Third, it decreases the number of twists by rewarding the situation where nonconsecutive AFPs share the same transformation in the alignment, which is realized by dynamic programming with an improved transition function. The experimental data show that compared with FlexProt, FATCAT, and FlexSnap, the proposed method can achieve comparable results by introducing fewer twists. Meanwhile, it can generate results similar to those of the FATCAT method in much less running time due to the reduced number of AFPs.

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A local average distance descriptor for flexible protein structure comparison

Cited by 7 publications

References 66 publications

Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study

Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study

Protein folding prediction in the HP model using ions motion optimization with a greedy algorithm

Using Variable-Length Aligned Fragment Pairs and an Improved Transition Function for Flexible Protein Structure Alignment

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