CHAPERONg: A tool for automated GROMACS-based molecular dynamics simulations and trajectory analyses.

Molecular dynamics (MD) simulation is a powerful computational tool used in biomolecular studies to investigate the dynamics, energetics, and interactions of a wide range of biological systems at the atomic level. GROMACS is a widely used free and open-source biomolecular MD simulation software recognized for its efficiency, accuracy, and extensive range of simulation options. However, the complexity of setting up, running, and analyzing MD simulations for diverse systems often poses a significant challenge, requiring considerable time, effort, and expertise. Here, we introduce CHAPERONg, a tool that automates the GROMACS MD simulation pipelines for protein and protein-ligand systems. CHAPERONg also integrates seamlessly with GROMACS modules and third-party tools to provide comprehensive analyses of MD simulation trajectories, offering up to 20 post-simulation processing and trajectory analyses. It also streamlines and automates established pipelines for conducting and analyzing biased MD simulations via the steered MD-umbrella sampling workflow. Thus, CHAPERONg makes MD simulations more accessible to beginner GROMACS users whilst empowering experts to focus on data interpretation and other less programmable aspects of MD simulation workflows. CHAPERONg is written in Bash and Python, and the source code is freely available at https://github.com/abeebyekeen/CHAPERONg. Detailed documentation and tutorials are available online at dedicated web pages accessible via https://abeebyekeen.com/chaperong-online.

Antidiarheal activity of catechol and ethyl 5, 8,11,14,17 - icosapentanoate-rich fraction of Annona senegalensis stem bark.

Background and aim: Secretory diarrhea is the most common type of diarrhea. This study aimed at exploring the possible mechanism of antisecretory action of Annona senegalensis stem bark and to identify the bioactive compounds. Experimental procedure: The ability of three crude extract; aqueous, dichloromethane and hexane stem bark extracts to inhibit castor oil-induced stooling in albino rats were assessed. Bioactivity guided fractionation of the most active extract was done using solvent-solvent partitioning (with hexane, dichloromethane, ethylacetate) and column chromatography. In vitro antioxidant activity of the most active sub-fraction was done using standard methods. The most active sub-fraction (25 mg/kg b. wt.) was administered to castor oil-induced diarrheal rats. Diarrheal rats small intestinal malondialdehyde concentration, antioxidant enzyme, cyclooxygenase II and Na+- K+ ATPase activities were determined using standard procedures. GC-MS analysis was done to identify the chemical compounds in the sub-fraction. Result and conclusion: Aqueous extract significantly decreased the number of wet stools. Sub-fraction 1 of ethylacetate fraction of aqueous stem bark extract (EFAS1) showed the highest stool inhibition. The H2O2 scavenging activity of EFAS1 was significantly greater than ascorbic acid. The sub-fraction significantly increased (p < 0.05) the activity of catalase and Na+- K+ ATPase activities but significantly decreased the concentration of malondialdehyde and cyclooxygenase II activity. GC-MS analysis revealed that EFAS1 is rich in catechol, n-hexadecanoic acid and ethyl-5,8,11,14,17-icosapentanoate. The sub-fraction exerts its antisecretory activity by its antioxidative, inhibition of prostaglandin synthesis and stimulation of Na+- K+ ATPase properties due to the presence of catechol, n-hexedecanoic acid and ethyl-5,8,11,14,17-icosapentanoate.

Synergistic enhancement of rat intestinal alkaline phosphatase activity by taurine and sodium butyrate protects against endotoxin-induced bowel inflammation.

The effect of sodium butyrate (SB) and taurine on rat intestinal alkaline phosphatase (RIA) and the effect of the interaction of taurine and/or SB with bacterial lipopolysaccharides on ALP activity were investigated. In vitro analysis of the activity of RIA was carried out using various concentrations of SB and/or taurine. Substrate concentration-dependent kinetic study was performed at 1-10 mM of taurine and SB at 5.17 mM of p-nitrophenyl phosphate (p-NPP). The in vivo effect of lipopolysaccharide (LPS) in the presence and absence of taurine and SB on the activity of RIA was also evaluated. LPS was administered to rats intraperitoneally and 20 min after; this was followed by oral administration of SB and/or taurine. The hydrolysis of p-NPP by RIA was enhanced by taurine and SB at different concentrations. The in vivo kinetic study revealed that RIA activity was greater (588.23 × 10-3  µmol/min/ml) when taurine and SB were co-administered with bacterial LPS, yielding a low Km (0.12 mM) value. This suggested an increased affinity for the substrate by the enzyme. The degree of activation was highest when SB and taurine were administered together with LPS. The study concluded that SB and taurine are activators of RIA and their positive synergistic interaction in the presence of bacterial LPS may further emphasize the role of both activators in attenuating bacterial LPS-mediated diseases. PRACTICAL APPLICATIONS: The development and progression of a myriad of diseases such as inflammatory bowel disease, atherosclerosis, sepsis, multiple sclerosis, and rheumatoid arthritis have been linked to bacterial endotoxin. Taurine is an amino acid derived from cysteine, while sodium butyrate is a short-chain fatty acid. Consumption of food and food supplement rich in taurine and sodium butyrate can help protect against endotoxemic injury and aid tissue repair in the small intestine, digestibility, growth, and overall health of animals.

Blood pressure and sugar regulating potentials of Anarcadium occidentale nut globulin and albumin hydrolysates.

Several novel functional peptides have been successfully extracted from plant storage proteins. This study investigated the degree of hydrolysis, peptide yield, amino acid constituents, angiotensin converting enzyme (ACE), alpha amylase inhibitory and in vitro antioxidant activities of cashew (Anarcardium occidentale) nut proteins (CNP) hydrolysates (CNPHs). Cashew nut proteins (albumin and globulin) were hydrolysed using pancreatin, Alcalase and trypsin. The peptide yield and degree of hydrolysis (DH) of CNP by pancreatin (75.69 ± 0.84%; 37.39 ± 0.31) was significantly higher than those by Alcalase (61.67 ± 0.55%; 23.87 ± 0.23) and trypsin (43.33 ± 0.45%; 11 ± 0.15). The inhibition of ACE by albumin and globulin hydrolysates was concentration dependent. At 1.2 mg/mL, ACE-inhibitory activity of pancreatic cashew nut globulin (CNGH) hydrolysate (51.65 ± 1.2%) was significantly higher than those of Alcalase (34.603 ± 0.65%) and tryptic (29.92 ± 0.73%) CNGHs. Cashew nut albumin hydrolysate (CNAH) demonstrated concentration-dependent alpha-amylase inhibition (IC50 0.17 ± 0.02-0.41 ± 0.021 mg/mL). The order of inhibition was tryptic > Alcalase > pancreatic CNAHs. The pancreatic hydrolysates of both albumin and globulin fractions displayed the highest DPPH antioxidant activity, while pancreatic CNAH was the most potent superoxide anion scavenger. These findings therefore posit that cashew nut globulin and albumin hydrolysates are laden with useful bioactive peptides that may be further explored for regulation of blood pressure and sugar in hypertensive and diabetic in vivo models.

In vitro Angiotesin-1-converting enzyme, α-amylase and α-glucosidase inhibitory and antioxidant activities of Luffa cylindrical (L.) M. Roem seed protein hydrolysate.

In recent times, researchers have explored food derived peptides to circumvent the side effects of synthetic drugs. This study therefore examined the amino acid constituents, in vitro antioxidant activities, angiotensin-1-converting enzyme (ACE), α-glucosidase and α-amylase inhibition kinetics of protein hydrolysate obtained from the seed of Luffa cylindrica. The peptide yield by pepsin (16.93 ± 0.28%) and trypsin (13.20 ± 1.02%) were significantly lower than that of Alcalase (34.04 ± 1.96%). Alcalase hydrolysate however displayed the highest ferric reducing antioxidant capacity (FRAC), 1,1-diphenyl-2-picrylhydrazyl (DPPH) and H2O2 scavenging activities (0.63%, 85.88% and 41.69% respectively), while the highest superoxide scavenging activity was shown by peptic hydrolysate (57.89%). The ACE inhibition by the hydrolysates with IC50 of 0.32-0.93 mg/mL, increased as the concentration of the peptic hydrolysate increased with the highest ACE-inhibitory activity (74.99 ± 0.43%) at 1.2 mg/mL of peptic hydrolysate. Tryptic and Alcalase hydrloysates exhibited a strong α-amylase inhibition having 27.96 ± 0.06% and 36.36 ± 0.71% inhibitory capacity respectively with IC50 of 1.02-3.31 mg/mL. Alcalase hydrolysates demonstrated the strongest inhibition (65.81 ± 1.95%), followed by tryptic hydrolysates (54.53 ± 0.52%) in a concentration-dependent inhibition of α-glucosidase (IC50 , 0.48-0.80 mg/mL). Kinetic analysis showed that ACE-inhibition by different concentrations of Alcalase, pepsin and trypsin hydrolysates is uncompetitive, mixed-type and non-competitive respectively. α-Amylase was non-competitively inhibited while α-glucosidase was un-competitively inhibited by all the hydrolysates. The total amino acid concentration for Alcalase, trypsin and pepsin hydrolysates was 53.51g/100g, 75.40g/100g and 85.42g/100g of Luffa cylindrica seed protein hydrolysate respectively, with glutamate being the most concentrated essential amino acid in all the three hydrolysates. From these results, it can be deduced that Luffa cylindrica seed Alcalase and tryptic protein hydrolysates may play critical and indispensible role as bio-tools in diabetes and hypertension treatment.