Showing papers by "Don Kulasiri published in 2023"

Proteins as fuzzy controllers: Auto tuning a biological fuzzy inference system to predict protein dynamics in complex biological networks

Abstract: Biological systems such as mammalian cell cycle are complex systems consisting of a large number of molecular species interacting in ways that produce complex nonlinear systems dynamics. Discrete models such as Boolean models and continuous models such as Ordinary Differential Equations (ODEs) have been widely used to study these systems. Boolean models are simple and can capture qualitative systems behaviour, but they cannot capture the continuous trends of protein concentrations, while ODE models capture continuous trends but require kinetics parameters that are limited. Further, as systems get larger, complexity of these models becomes an issue for parameterization, analysis and interpretation. Also, molecular systems operate under the conditions of uncertainty and noise and our understanding of molecular processes in general is more at a qualitative level characterised by vagueness, imprecision and ambiguity. Hence, as more data are generated, there is a greater need for simpler data driven methods that can approximate continuous system behaviour while representing vagueness and ambiguity without requiring kinetic parameters. Fuzzy inferencing is one such promising method with the ability to work with qualitative vague/imprecise biological knowledge. In this study, we propose a fuzzy inference system for representing continuous behaviour of proteins and apply to some key proteins in the mammalian cell cycle system. The methods we introduced here is novel to protein interaction systems and cell cycle proteins. Our study proposes a three-stage approach to develop fuzzy protein controllers. In stage one, protein system is studied for interactions. We studied some significant core controllers of mammalian cell cycle and their producers and degraders as presented in a published ODE model. Based on the observations from a dataset generated from it, we developed Fuzzy inference systems (FIS) in the second stage, that involved deriving fuzzy IF-THEN rules and their processing, and manually tuned the FIS to predict the dynamics of individual proteins. In stage three, we employed Particle Swarm Optimisation (PSO) for optimising the FIS to further enhance prediction accuracy. Systems dynamics simulation results of the optimised FIS models were in close agreement with the benchmark ODE model results. The results show that the FIS models provide a close approximation to the comprehensive benchmark model in robustly representing continuous protein dynamics while representing the control of protein behavior in an intuitive and transparent format without requiring kinetic parameters. Therefore, FIS models can be an alternative to ODEs in network modelling. Further, FIS models can be assembled to develop large complex systems without losing information or accuracy.

Alleviating the unwanted effects of oxidative stress on Aβ clearance: a review of related concepts and strategies for the development of computational modelling

Abstract: Treatment for Alzheimer's disease (AD) can be more effective in the early stages. Although we do not completely understand the aetiology of the early stages of AD, potential pathological factors (amyloid beta [Aβ] and tau) and other co-factors have been identified as causes of AD, which may indicate some of the mechanism at work in the early stages of AD. Today, one of the primary techniques used to help delay or prevent AD in the early stages involves alleviating the unwanted effects of oxidative stress on Aβ clearance. 4-Hydroxynonenal (HNE), a product of lipid peroxidation caused by oxidative stress, plays a key role in the adduction of the degrading proteases. This HNE employs a mechanism which decreases catalytic activity. This process ultimately impairs Aβ clearance. The degradation of HNE-modified proteins helps to alleviate the unwanted effects of oxidative stress. Having a clear understanding of the mechanisms associated with the degradation of the HNE-modified proteins is essential for the development of strategies and for alleviating the unwanted effects of oxidative stress. The strategies which could be employed to decrease the effects of oxidative stress include enhancing antioxidant activity, as well as the use of nanozymes and/or specific inhibitors. One area which shows promise in reducing oxidative stress is protein design. However, more research is needed to improve the effectiveness and accuracy of this technique. This paper discusses the interplay of potential pathological factors and AD. In particular, it focuses on the effect of oxidative stress on the expression of the Aβ-degrading proteases through adduction of the degrading proteases caused by HNE. The paper also elucidates other strategies that can be used to alleviate the unwanted effects of oxidative stress on Aβ clearance. To improve the effectiveness and accuracy of protein design, we explain the application of quantum mechanical/molecular mechanical approach.

Complexation of starch and phenolic compounds during food processing and impacts on the release of phenolic compounds.

Abstract: Phenolic compounds can form complexes with starch during food processing, which can modulate the release of phenolic compounds in the gastrointestinal tract and regulate the bioaccessibility of phenolic compounds. The starch-phenolic complexation is determined by the structure of starch, phenolic compounds, and the food processing conditions. In this review, the complexation between starch and phenolic compounds during (hydro)thermal and nonthermal processing is reviewed. A hypothesis on the complexation kinetics is developed to elucidate the mechanism of complexation between starch and phenolic compounds considering the reaction time and the processing conditions. The subsequent effects of complexation on the physicochemical properties of starch, including gelatinization, retrogradation, and digestion, are critically articulated. Further, the release of phenolic substances and the bioaccessibility of different types of starch-phenolics complexes are discussed. The review emphasizes that the processing-induced structural changes of starch are the major determinant modulating the extent and manner of complexation with phenolic compounds. The controlled release of complexes formed between phenolic compounds and starch in the digestive tracts can modify the functionality of starch-based foods and, thus, can be used for both the modulation of glycemic response and the targeted delivery of phenolic compounds.