MyMedR

Displaying all 5 publications

Abstract:

Sort:

Fulltext In silico design of potentially functional artificial metallo-haloalkane dehalogenase containing catalytic zinc

Ang TF, Salleh AB, Normi YM, Leow TC

3 Biotech, 2018 Jul;8(7):314.
PMID: 30023146 DOI: 10.1007/s13205-018-1333-9

Artificial metalloenzymes are unique as they combine the good features of homogeneous and enzymatic catalysts, and they can potentially improve some difficult catalytic assays. This study reports a method that can be used to create an artificial metal-binding site prior to proving it to be functional in a wet lab. Haloalkane dehalogenase was grafted into a metal-binding site to form an artificial metallo-haloalkane dehalogenase and was studied for its potential functionalities in silico. Computational protocols regarding dynamic metal docking were studied using native metalloenzymes and functional artificial metalloenzymes. Using YASARA Structure, a simulation box covering template structure was created to be filled with water molecules followed by one mutated water molecule closest to the metal-binding site to metal ion. A simple energy minimization step was subsequently run using an AMBER force field to allow the metal ion to interact with the metal-binding residues. Long molecular dynamic simulation using YASARA Structure was performed to analyze the stability of the metal-binding site and the distance between metal-binding residues. Metal ions fluctuating around 2.0 Å across a 20 ns simulation indicated a stable metal-binding site. Metal-binding energies were predicted using FoldX, with a native metalloenzyme (carbonic anhydrase) scoring 18.0 kcal/mol and the best mutant model (C1a) scoring 16.4 kcal/mol. Analysis of the metal-binding site geometry was performed using CheckMyMetal, and all scores for the metalloenzymes and mutant models were in an acceptable range. Like native metalloenzymes, the metal-binding site of C1a was supported by residues in the second coordination shell to maintain a more coordinated metal-binding site. Short-chain multihalogenated alkanes (1,2-dibromoethane and 1,2,3-trichloropropane) were able to dock in the active site of C1a. The halides of the substrate were in contact with both the metal and halide-stabilizing residues, thus indicating a better stabilization of the substrate. The simple catalytic mechanism proposed is that the metal ion interacted with halogen and polarized the carbon-halogen bond, thus making the alpha carbon susceptible to attack by nucleophilic hydroxide. The interaction between halogen in the metal ion and halide-stabilizing residues may help to improve the stabilization of the substrate-enzyme complex and reduce the activation energy. This study reports a modified dynamic metal-docking protocol and validation tests to verify the metal-binding site. These approaches can be applied to design different kinds of artificial metalloenzymes or metal-binding sites.
Fulltext Dehalogenases: From Improved Performance to Potential Microbial Dehalogenation Applications

Ang TF, Maiangwa J, Salleh AB, Normi YM, Leow TC

Molecules, 2018 05 07;23(5).
PMID: 29735886 DOI: 10.3390/molecules23051100

The variety of halogenated substances and their derivatives widely used as pesticides, herbicides and other industrial products is of great concern due to the hazardous nature of these compounds owing to their toxicity, and persistent environmental pollution. Therefore, from the viewpoint of environmental technology, the need for environmentally relevant enzymes involved in biodegradation of these pollutants has received a great boost. One result of this great deal of attention has been the identification of environmentally relevant bacteria that produce hydrolytic dehalogenases—key enzymes which are considered cost-effective and eco-friendly in the removal and detoxification of these pollutants. These group of enzymes catalyzing the cleavage of the carbon-halogen bond of organohalogen compounds have potential applications in the chemical industry and bioremediation. The dehalogenases make use of fundamentally different strategies with a common mechanism to cleave carbon-halogen bonds whereby, an active-site carboxylate group attacks the substrate C atom bound to the halogen atom to form an ester intermediate and a halide ion with subsequent hydrolysis of the intermediate. Structurally, these dehalogenases have been characterized and shown to use substitution mechanisms that proceed via a covalent aspartyl intermediate. More so, the widest dehalogenation spectrum of electron acceptors tested with bacterial strains which could dehalogenate recalcitrant organohalides has further proven the versatility of bacterial dehalogenators to be considered when determining the fate of halogenated organics at contaminated sites. In this review, the general features of most widely studied bacterial dehalogenases, their structural properties, basis of the degradation of organohalides and their derivatives and how they have been improved for various applications is discussed.
Fulltext An Adaptive Wake-Up-Interval to Enhance Receiver-Based Ps-Mac Protocol for Wireless Sensor Networks

Adam MS, Por LY, Hussain MR, Khan N, Ang TF, Anisi MH, et al.

Sensors (Basel), 2019 Aug 29;19(17).
PMID: 31470520 DOI: 10.3390/s19173732

Many receiver-based Preamble Sampling Medium Access Control (PS-MAC) protocols have been proposed to provide better performance for variable traffic in a wireless sensor network (WSN). However, most of these protocols cannot prevent the occurrence of incorrect traffic convergence that causes the receiver node to wake-up more frequently than the transmitter node. In this research, a new protocol is proposed to prevent the problem mentioned above. The proposed mechanism has four components, and they are Initial control frame message, traffic estimation function, control frame message, and adaptive function. The initial control frame message is used to initiate the message transmission by the receiver node. The traffic estimation function is proposed to reduce the wake-up frequency of the receiver node by using the proposed traffic status register (TSR), idle listening times (ILTn, ILTk), and "number of wake-up without receiving beacon message" (NWwbm). The control frame message aims to supply the essential information to the receiver node to get the next wake-up-interval (WUI) time for the transmitter node using the proposed adaptive function. The proposed adaptive function is used by the receiver node to calculate the next WUI time of each of the transmitter nodes. Several simulations are conducted based on the benchmark protocols. The outcome of the simulation indicates that the proposed mechanism can prevent the incorrect traffic convergence problem that causes frequent wake-up of the receiver node compared to the transmitter node. Moreover, the simulation results also indicate that the proposed mechanism could reduce energy consumption, produce minor latency, improve the throughput, and produce higher packet delivery ratio compared to other related works.
Factors influencing healthcare seeking in patients with dengue: Systematic review

Ng TC, Teo CH, Toh JY, Dunn AG, Ng CJ, Ang TF, et al.

Trop Med Int Health, 2022 Jan;27(1):13-27.
PMID: 34655508 DOI: 10.1111/tmi.13695

OBJECTIVE: Delays in seeking healthcare for dengue are associated with poor health outcomes. Despite this, the factors influencing such delays remain unclear, rendering interventions to improve healthcare seeking for dengue ineffective. This systematic review aimed to synthesise the factors influencing healthcare seeking of patients with dengue and form a comprehensive framework.
METHODS: This review included both qualitative and quantitative studies. Studies were obtained by searching five databases, contacting field experts and performing backward reference searches. The best-fit meta-synthesis approach was used during data synthesis, where extracted data were fitted into the social-ecological model. Sub-analyses were conducted to identify the commonly reported factors and their level of statistical significance.
RESULTS: Twenty studies were selected for meta-synthesis. Eighteen factors influencing healthcare seeking in dengue were identified and categorised under four domains: individual (11 factors), interpersonal (one factor), organisational (four factors) and community (two factors). The most reported factors were knowledge of dengue, access to healthcare, quality of health service and resource availability. Overall, more barriers to dengue health seeking than facilitators were found. History of dengue infection and having knowledge of dengue were found to be ambiguous as they both facilitated and hindered dengue healthcare seeking. Contrary to common belief, women were less likely to seek help for dengue than men.
CONCLUSIONS: The factors affecting dengue healthcare-seeking behaviour are diverse, can be ambiguous and are found across multiple social-ecological levels. Understanding these complexities is essential for the development of effective interventions to improve dengue healthcare-seeking behaviour.
Feasibility and acceptability of a dengue self-monitoring system to reduce treatment delay in Malaysia: A single-centre pilot randomised controlled trial

Ng WL, Ng CJ, Teo CH, Ang TF, Lee YK, Abdul Hadi H, et al.

Digit Health, 2024;10:20552076241277710.
PMID: 39247097 DOI: 10.1177/20552076241277710

OBJECTIVE: Most dengue cases are managed in an outpatient setting, where patients are advised to return to the clinic daily for monitoring. Some patients can develop severe dengue at home and fail to recognise the deterioration. An application called DengueAid was designed as a self-monitoring tool for patients to reduce delay in seeking timely treatment. This study aimed to assess the feasibility of conducting a randomised controlled trial to determine the effectiveness of the DengueAid application.
METHODS: Dengue patients were recruited from a public health clinic in Malaysia and randomised to either use the DengueAid application plus standard care for dengue or receive only the standard care. The outcomes evaluated were the (1) feasibility of recruitment, data collection and follow-up procedures; (2) preliminary clinical outcome measures; and (3) acceptability of DengueAid. Qualitative interviews were conducted for participants in the intervention arm to assess the acceptability of DengueAid.
RESULTS: Thirty-seven patients were recruited with 97% (n = 36) retention rates. The recruitment rate was low (63% refusal rate, n = 62/99) with difficulty in data collection and follow-up due to the variable interval of care for dengue in an outpatient setting. DengueAid application was acceptable to the participants, but preliminary clinical outcomes and qualitative data suggested limited utility of the application. Unwell conditions of patients and limited access to healthcare are important factors impacting the application's utility.
CONCLUSION: The feasibility trial uncovered issues with recruitment, data collection and follow-up processes. Further research and modification to the application are needed to improve its utility and usability.