Jornal de Ciência da Computação e Biologia de Sistemas

We describe a novel way of applying Chaos Game Representation (CGR) method to protein sequences of different families by considering the amino acids into three secondary structure groups of residues. The present study to identify the patterns of the secondary structure of family of protein sequences for different ratios and to analyze to apply CGR method to protein structures, so as to find out any intrinsic self-similar pattern exhibited in the CGR plot. Further, we find that the sequences of different protein families belonging to all the four major structural classes namely, all α, all β, α plus β and α by β produce a similar kind of self-similar fractal structure. In a broader sense, is there any way to obtain a single graphical representation depicting any intrinsic self-similar pattern exhibited by the different protein families?

Thyroid hormone secretion pathway is one of the important pathways that regulates growth, development and is considered critical for brain, skeletal development and maturation. Autoimmune Thyroid Disease (AITD) results in damage of the thyroid gland altering the normal secretion of thyroid hormones causing hypothyroidism (Hashimoto’s thyroiditis) or hyperthyroidism (graves’ disease). A map of molecular interaction of the thyroid stimulating hormone receptor has been created using systems biology graphical notation language with the help of CellDesigner 4.1 and converted into BioPax 2.8.2 pathways description format. In the current state the map contains 9 compartment, 32 simple and complex protein, 18 small molecules, 3 ions and 35 chemical reactions. The network contains more details about Thyroid hormones, Thyroxin (T4) and Triiodothyronin (T3), secretion pathway than existing large scale real pathways. Simulation was done in order to understand the time-dependent behavior of TSH, T3 and T4 by taking 16 different cases related thyroid disorder. The simulation patterns are invariable after passing with certain period, it does not deviate the simulation pattern of pathways. This study helps in identification of novel targets related with different types of thyroid disorder. To anticipate potential drug targets by system-wide analysis of the metabolic network for the effective treatment of thyroid disorder, the model can be useful.

Consensus approach is an efficient strategy to identify hot residue important for compactness and stability of protein. Structure of ARM lipase was modeled to explore the possible effect of critical point mutation towards structure and function. The significant difference of amino acid at position 157 between ARM lipase (Arg157) and other thermostable lipases (Ser157) was targeted as a critical residue. Using YASARA software, Arg157 was substituted to Ser and subsequently the energy minimized. Both ARM and R157S lipases were analyzed by MD simulations at different temperatures (50ºC,60ºC, and 70ºC). MD simulation result showed that R157S lipase had lower value of RMSD, RMSF, solvent accessible surface area (SASA) and radius of gyration than native ARM lipase. It indicated that R157S lipase had higher compactness in the structure leading to enhanced stability. To validate the computational data, the substitution of Arg157 to Ser has been conducted using site-directed mutagenesis experimentally. The catalytic efficiency (kcat/KM) of R157S lipase was refold better than ARM lipase of 70°C. Circular dichorism study revealed that R157S lipase had increased thermostability with higher Tm value (71.6°C) than its wildtype (63.9°C) indicating a better compactness as revealed by spectrofluorocence study. Thus the rational design of substituting Arg157 with Ser improved the protein folding of mutant lipase as shown in MD simulations and subsequently increased the catalytic effectiveness and thermodynamic stability.

Great demand for plant starch has made starch biosynthesis one of the most studied pathways in the literature. Many attempts have been made to improve the yield and properties of starch, including research on CO2 elevation as a means of increasing production; however, the analyses often faced difficulty in transiently and simultaneously measuring the metabolites of interest. Our work aimed to break-through such restrictions by systematically investigating the changes in metabolism of starch throughout the pathway-from source to sink cells-with the aid of mathematical modelling. Monitoring changes in metabolite concentrations and flux distributions allowed us to propose a formal metabolic path (i.e. a preferential pathway in charge of a particular event) responsible for starch yield variation under excess carbon-substrate. Our findings not only supported many established hypotheses on the regulations of starch production, but also gave reasonable predictions of metabolic regulation of starch biosynthesis.