Molecular Modeling Research Articles

Maple syrup urine disease diagnosis in Brazilian patients by massive parallel sequencing

Biallelic pathogenic variants cause maple syrup urine disease (MSUD) in one of the branched-chain α-keto acid dehydrogenase (BCKDH) complex genes (BCKDHA, BCKDHB, DBT, DLD, and PPM1K) leading to the accumulation of leucine, isoleucine, and valine. This study aimed to perform a molecular diagnosis of Brazilian patients with MSUD using gene panels and massive parallel sequencing. Eighteen Brazilian patients with a biochemical diagnosis of MSUD were analyzed by massive parallel sequencing in the Ion PGM Torrent Server using a gene panel with the BCKDHA, BCKDHB, and DBT genes. The American College of Medical Genetics and Genomics guidelines were used to determine variant pathogenicity. Thirteen patients had both variants found by massive parallel sequencing, whereas 3 patients had only one variant found. In 2 patients, the variants were not found by this analysis. These 5 patients required additional Sanger sequencing to confirm their genotype. Twenty-five pathogenic variants were identified in the 3 MSUD-related genes (BCKDHA, BCKDHB, and DBT). Most variants were present in the BCKDHB gene, and no common variants were found. Nine novel variants were observed: c.922 A > G, c.964C > A, and c.1237 T > C in the BCKDHA gene; and c.80_90dup, c.384delA, c.478 A > T, c.528C > G, c.977 T > C, and c.1039-2 A > G in the BCKDHB gene. All novel variants were classified as pathogenic. Molecular modeling of the novel variants indicated that the binding of monomers was affected in the BCKDH complex tetramer, which could lead to a change in the stability and activity of the enzyme. Massive parallel sequencing with targeted gene panels seems to be a cost-effective method that can provide a molecular diagnosis of MSUD.

Identification of a novel RHCE*Ce (829G > A) allele associated with absence of C and e antigens expression.

The Rh blood group antigens are encoded by the RHD and RHCE genes, which possess a remarkable degree of polymorphism owing to their high homologous structures. These variants of the RH genes can lead to absence or weak expression of antigens. Analysis of RHCE genotyping by Polymerase Chain Reaction (PCR-SSP) method specific to detect c.48G, c.48C, 109 bp insertion of IVS2, c.201A and c.307C and RhCE phenotyping, were conducted in 316 Chinese patients in previous study. One patient with discrepancy typing result was collected for further RhCE serologic typing using microcolumn gel method and tube method in saline using monoclonal antibodies. PacBio sequencing was performed for RHCE, RHD and RHAG complete sequence analysis. 3D molecular models of the protein with the wild-type and mutant residue were generated using the DynaMut web server. The effect of the mutation on the protein function was predicted by PolyPhen-2 software. One male patient of Chinese Han was detected with RHCE*C allele showed by PCR-SSP method but ccEE phenotype. Further PacBio sequencing identified one normal RHCE*cE allele and one RHCE*Ce allele carried a novel c.829G > A (p.Gly277Arg) variant, which the encoded amino acid located in the ninth transmembrane segment of RhCE protein. Crystallisation analysis of 3D molecular models revealed that the substitution at Arg277 leads to the formation of additional hydrogen bonds, including weak hydrogen bonds between multiple atoms. It also results in hydrophobic ion interactions between Arg277 and Ala244. This mutation is predicted to have a damaging effect on protein function. One novel RHCE*Ce allele with c.829G > A (p.Gly277Arg) variant was identified to resulting in the absence or weak expression of C and e antigens.

Molecular Modeling Studies to mimic the Binding Hypothesis of NEU3 Sialidase aand EGFR in Non-small Cell Lung Carcinoma

Molecular Modeling Studies to mimic the Binding Hypothesis of NEU3 Sialidase aand EGFR in Non-small Cell Lung Carcinoma

Molecular Modeling Methods in the Development of Affine and Specific Protein-Binding Agents.

High-affinity and specific agents are widely applied in various areas, including diagnostics, scientific research, and disease therapy (as drugs and drug delivery systems). It takes significant time to develop them. Forthis reason, development of high-affinity agents extensively utilizes computer methods at various stages for the analysis and modeling of these molecules. The review describes the main affinity and specific agents, such as monoclonal antibodies and their fragments, antibody mimetics, aptamers, and molecularly imprinted polymers. The methods of their obtaining as well as their main advantages and disadvantages are briefly described, with special attention focused on the molecular modeling methods used for their analysis and development.

Dependence of the mechanical responses on crumpled-foil textures in C-S-H nanostructure sheets

Calcium silicate hydrate (C-S-H) is a significant hydration product in cementitious materials which plays a significant role in contributing to cohesive strength and properties of cementitious materials. Despite numerous studies, the failure mechanism of C-S-H gels remains uncovered. In this study, we explored the complex failure mechanisms of C-S-H sheets at different angular configurations. Our research unveils the intricate relationship between these mechanisms and the structural configurations and external loading conditions. Notably, we have observed that C-S-H sheets exhibit enhanced cohesion under specific configurations, while such enhancement is absent in alternative scenarios. This study demonstrates the nuanced behavior of C-S-H sheets under varying loads, underscoring the pivotal role played by angular configurations in shaping their failure mechanisms. These insights not only contribute to the development of coarse-grained molecular models for C-S-H but also provide valuable guidance for further research about the failure mechanism of the cement-based materials.

Unveiling Therapeutic Avenues for Crohn's Disease Management: Exploring Inhibitors for Adherent-Invasive Escherichia coli Propanediol Dehydratase.

Inflammatory Bowel Disease (IBD) encompasses a group of chronic disorders distinguished by inflammation of the gastrointestinal tract. Among these, Crohn's Disease (CD) stands out as a complex and impactful condition due to challenges for both diagnosis and management, making it a cynosure of research. In CD, there is the predominance of proinflammatory bacteria, including the Adherentinvasive Escherichia coli (AIEC) with virulence-associated metabolic enzyme Propanediol Dehydratase (pduC), which has been identified as a therapeutic target for the management of CD. Herein, molecular modeling techniques, including molecular docking, Molecular Mechanics with Generalized Born and Surface Area (MMGBSA), drug-likeness, and pharmacokinetics profiling, were utilized to probe the potentials of eighty antibacterial compounds to serve as inhibitors of pduC. The results of this study led to the identification of five compounds with promising potentials; the results of the molecular docking simulation revealed the compounds as possessing better binding affinities for the target compared to the standard drug (sulfasalazine), while Lipinski's rule of five-based assessment of their drug-likeness properties revealed them as potential oral drugs. MMGBSA free energy calculation and Molecular Dynamics (MD) simulation of the complexes formed a sequel to molecular docking, revealing the compounds as stable binders in the active site of the protein. Ultimately, the results of this study have revealed five compounds to possess the potential to serve as inhibitors of pduC of AIEC. However, experimental studies are still needed to validate the findings of this study.

Discovery of Novel Isatin Encompassing Oxadiazoles as Potential Inhibitors against New Delhi Metallo-β-lactamase-1: Synthesis, Spectral Analysis, Antimicrobial, and Molecular Modeling Studies

Discovery of Novel Isatin Encompassing Oxadiazoles as Potential Inhibitors against New Delhi Metallo-β-lactamase-1: Synthesis, Spectral Analysis, Antimicrobial, and Molecular Modeling Studies

Revolutionizing Drug Discovery: A Comprehensive Review of Computer-Aided Drug Design Approaches

Abstract: Computer-Aided Drug Design (CADD) has significantly advanced the drug discovery process, offering tools to enhance efficiency and reduce costs. This review explores essential CADD methodologies, including molecular docking, virtual screening, ADMET profiling, homology modeling, and Quantitative Structure-Activity Relationship (QSAR) models. Molecular docking predicts interactions between drugs and targets, while virtual screening evaluates large compound libraries to identify promising candidates. ADMET profiling assesses pharmacokinetic and toxicological properties early in development. Homology modeling constructs three-dimensional protein models to aid target identification, and QSAR models predict biological activities based on chemical structures. These integrated approaches streamline drug development, providing a robust framework for modern pharmaceutical research.

Multi-Template-Guided Synthesis of High-Dimensional Molecular Assemblies for Humidity Gradient-Based Power Generators.

Systematically orchestrating fundamental building blocks into intricate high-dimensional molecular assemblies at molecular level is imperative for multifunctionality integration. However, this remains a formidable task in crystal engineering due to the dynamic nature of inorganic building blocks. Herein, we develop a multi-template-guided strategy to control building blocks. The coordination modes of ligands and the spatial hindrance of anionic templates are pivotal in dictating the overall structures. Flexible multi-dentate linkers selectively promote the formation of oligomeric assembly ([TeO3(Mo2O2S2)3O2(OH)(C5O2H7)3]4- {TeMo6}) into tetrahedral cages ([(TeO3)4(Mo2O2S2)12(OH)12(C9H9O4P)6]8- {Te4Mo24} and [(AsO4)4(Mo2O2S2)12(OH)12(C9H9O6)4]12- {As4Mo24}), while steric hindrance from anionic templates further assists in assembling cages into an open quadruply twisted Möbius nanobelt ([(C6H5O3P)8(Mo2O2S2)24(OH)24(C8H10O4)12]16- {P8Mo48}). Among these structures, the hydrophilic-hydrophobic hybrid cage {Te4Mo24} emerges as an exemplary molecular model for proton conduction and serves as a prototype for humidity gradient-based power generators (HGPGs). The Te4Mo24-PVDF-based HGPG (PVDF = Poly(vinylidene fluoride)) exhibits notable stability and power generation, yielding an open-circuit voltage of 0.51 V and a current density of 77.8 nA cm-2 at room temperature and 90% relative humidity (RH). Further insights into the interactions between water molecules and microscale molecules within the generator are achieved through molecular dynamics simulations. This endeavor unveils a universal strategy for synthesizing multifunctional integration molecules.

Multi‐Template‐Guided Synthesis of High‐Dimensional Molecular Assemblies for Humidity Gradient‐Based Power Generators

Systematically orchestrating fundamental building blocks into intricate high‐dimensional molecular assemblies at molecular level is imperative for multifunctionality integration. However, this remains a formidable task in crystal engineering due to the dynamic nature of inorganic building blocks. Herein, we develop a multi‐template‐guided strategy to control building blocks. The coordination modes of ligands and the spatial hindrance of anionic templates are pivotal in dictating the overall structures. Flexible multi‐dentate linkers selectively promote the formation of oligomeric assembly ([TeO3(Mo2O2S2)3O2(OH)(C5O2H7)3]4‐ {TeMo6}) into tetrahedral cages ([(TeO3)4(Mo2O2S2)12(OH)12(C9H9O4P)6]8‐ {Te4Mo24} and [(AsO4)4(Mo2O2S2)12(OH)12(C9H9O6)4]12‐ {As4Mo24}), while steric hindrance from anionic templates further assists in assembling cages into an open quadruply twisted Möbius nanobelt ([(C6H5O3P)8(Mo2O2S2)24(OH)24(C8H10O4)12]16‐ {P8Mo48}). Among these structures, the hydrophilic‐hydrophobic hybrid cage {Te4Mo24} emerges as an exemplary molecular model for proton conduction and serves as a prototype for humidity gradient‐based power generators (HGPGs). The Te4Mo24‐PVDF‐based HGPG (PVDF = Poly(vinylidene fluoride)) exhibits notable stability and power generation, yielding an open‐circuit voltage of 0.51 V and a current density of 77.8 nA cm‐2 at room temperature and 90% relative humidity (RH). Further insights into the interactions between water molecules and microscale molecules within the generator are achieved through molecular dynamics simulations. This endeavor unveils a universal strategy for synthesizing multifunctional integration molecules.

In silico insights into the design of novel NR2B-selective NMDA receptor antagonists: QSAR modeling, ADME-toxicity predictions, molecular docking, and molecular dynamics investigations

Based on a structural family of thirty-two NR2B-selective N-Methyl-D-Aspartate receptor (NMDAR) antagonists, two phenylpiperazine derivatives labeled C37 and C39 were conceived thanks to molecular modeling techniques, as novel NMDAR inhibitors exhibiting the highest analgesic activities (of pIC50 order) against neuropathic pain, with excellent ADME-toxicity profiles, and good levels of molecular stability towards the targeted protein of NMDA receptor. Initially, the quantitative structure-activity relationships (QSARs) models were developed using multiple linear regression (MLR), partial least square regression (PLSR), multiple non-linear regression (MNLR), and artificial neural network (ANN) techniques, revealing that analgesic activity was strongly correlated with dipole moment, octanol/water partition coefficient, Oxygen mass percentage, electronegativity, and energy of the lowest unoccupied molecular orbital, whose the correlation coefficients of generated models were: 0.860, 0.758, 0.885 and 0.977, respectively. The predictive capacity of each model was evaluated by an external validation with correlation coefficients of 0.703, 0.851, 0.778, and 0.981 respectively, followed by a cross-validation technique with the leave-one-out procedure (CVLOO) with Q2cv of 0.785, more than Y-randomization test, and applicability domain (AD), in addition to Fisher’s and Student’s statistical tests. Thereafter, ten novel molecules were designed based on MLR QSAR model, then predicted with their ADME-Toxicity profiles and subsequently examined for their similarity to the drug candidates. Finally, two of the most active compounds (C37 and C39) were chosen for molecular docking and molecular dynamics (MD) investigations during 100 ns of MD simulation time in complex with the targeted protein of NMDA receptor (5EWJ.pdb).

Halogen Bonding Hot Spots as a Constraint in Virtual Screening: A Case Study of 5-HT7R.

The recently developed and used molecular modeling approach to search for privileged amino acids for halogen bonding (XB hot spots) through XSAR sets has been applied to 5-HT7R. Herein, among all identified 5-HT7R XB hot spots, the S5x42 was employed in a virtual screening protocol as a constraint. Through a designed virtual screening protocol, 63 XSAR sets (156 compounds) were selected from more than 8 million commercially available compounds and examined using in vitro assay toward 5-HT7R. A 68% accuracy was found in predicting halogenated derivatives with higher affinity for 5-HT7R than their unsubstituted analogs. Moreover, it was observed that a halogen bond formed between S5x42 and a chlorine atom at the 3-position of the arylpiperazine fragment caused the most remarkable, 35.4-fold increase in binding affinity for 5-HT7R when compared to the nonhalogenated analog. Interestingly, molecular dynamics simulations showed the formation of a bifurcated halogen bond with S5x42.

Possibility for Exploitation and Identification of Rice Yield and Seed Quality Orthologs in Peanut (Arachis hypogaea L.)

Background: The advancement in gene tagging and mapping in model crops such as Arabidopsis, rice andmaize has outpaced progress in major legume crops like groundnut, chickpea, redgram, greengram andsoybean, even in the post-genome release period of legume databases. To address this gap, a study investigated the transferability of gene tagged markers (GTMs) associated with rice yield, grain size andmicronutrient content (Fe and Zn) to groundnut. Methods: This study utilized 17 diverse groundnut genotypes for molecular analysis, targeting 45 GTMs spanning 24 known functional genes. Result: Remarkably, 31 out of the 45 markers (76%) demonstrated high transferability to groundnut, indicating significant conservation in functional regions across species. The amplification efficiency of rice GTMs varied among groundnut genotypes, ranging from 79.17% to 91.67%. Notably, 17 markers targeting 14 rice genes showed amplification across all 17 groundnut genotypes (100%) studied. These findings underscore the potential of leveraging knowledge from functionally characterized genes in molecular model crops and annotated orthologous genes in ‘Omics’ databases to enhance gene tagging efforts in crops like groundnut. By harnessing this approach, there is an opportunity to expand the molecular-level tagging of genes and improve crops like groundnut, which have seen limited progress in gene tagging. This strategy opens avenues for pyramiding desirable genes with precision, thereby enhancing crop traits with greater accuracy.

Temperature effects on the sheath-core bar interface of composite insulators: a molecular dynamics and DFT study

The functioning condition of composite insulators is greatly influenced by the sheath-mandrel interface. In this work, the effects of temperature on the sheath-mandrel system are examined using molecular modeling, taking into account both density functional theory (DFT) and molecular dynamics (MD). The system’s interfacial free volume, HOMO/LUMO, number of hydrogen bonds, bond order, center-of-mass distance, and other characteristics define its degradation mechanism. The findings demonstrate that elevated temperatures have the potential to increase the interfacial free volume, the center-of-mass distance, and significantly reduce the number of hydrogen bonds. In addition, DFT simulations show that the bonding strength and non-bonding forces between the interfaces weaken with increasing temperature. High temperatures significantly boost the reactivity of the epoxy resin and silicone rubber chains, indicating that the system’s response with some intruders will be catalyzed by the temperature increase. This work looks at the temperature dependence of the sheath-core bar interface degradation from a microscopic perspective, which is important for enhancing the overall performance of composite insulators.

Investigation of tribological behavior of polytetrafluoroethylene/graphene composite

AbstractIn this study, we constructed molecular friction models for polytetrafluoroethylene (PTFE)/graphene composites with various defect ratios to represent their different wear stages and simulated their friction processes under different load conditions. The friction and wear mechanisms were revealed by analyzing the variations in their molecular architectures and energies during friction. The results indicate that the friction coefficient decreased with increasing load. When the load was constant, the friction coefficients of the composites containing defections were resemble, indicating that they remained unchanged in the different wear stages. The composite wear continued to increase during friction. However, the wear increment decreased gradually. In addition, by analyzing the changes in MSD, wear can be divided into initial, stable, and accelerated wear stages.Highlights Construct PTFE/Gr molecular models to represent their different wear stages. Simulate the dynamic changes of PTFE/Gr molecular structure during friction. The influence of PTFE/Gr dynamic structural changes was revealed. Reveal the normal force variation from an energy perspective.

Combatting Antibiotic-Resistant Staphylococcus aureus: Discovery of TST1N-224, a Potent Inhibitor Targeting Response Regulator VraRC, through Pharmacophore-Based Screening and Molecular Characterizations.

Staphylococcus aureus (S. aureus) is a major global health concern, causing various infections and presenting challenges due to antibiotic resistance. In particular, methicillin-resistant S. aureus, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus pose significant obstacles in treating S. aureus infections. Therefore, the critical need for novel drugs to counter these resistant forms is pressing. Two-component systems (TCSs), integral to bacterial regulation, offer promising targets for disruption. In this study, a comprehensive approach, involving pharmacophore-based inhibitor screening, along with biochemical and biophysical analyses were conducted to identify, characterize, and validate potential inhibitors targeting the response regulator VraRC of S. aureus. The constructed pharmacophore model, Phar-VRPR-N3, demonstrated effectiveness in identifying a potent inhibitor, TST1N-224 (IC50 = 60.2 ± 4.0 μM), against the formation of the VraRC-DNA complex. Notably, TST1N-224 exhibited strong binding to VraRC (KD = 23.4 ± 1.2 μM) using a fast-on-fast-off binding mechanism. Additionally, NMR-based molecular modeling revealed that TST1N-224 predominantly interacts with the α9- and α10-helixes of the DNA-binding domain of VraR, where the interactive and functionally essential residues (N165, K180, S184, and R195) act as hotspots for structure-based inhibitor optimization. Furthermore, TST1N-224 evidently enhanced the susceptibility of VISA to both vancomycin and methicillin. Importantly, TST1N-224 distinguished by 1,2,5,6-tetrathiocane with the 3 and 8 positions modified with ethanesulfonates holds significant potential as a lead compound for the development of new antimicrobial agents.

Aggregation behaviour of paraffin molecules with different branched distributions during crude oil gelling: A molecular dynamics study

Revealing the microdynamic mechanism and thermodynamic properties of the gelling process of waxy crude oil at the microscale plays an important role in ensuring the safe production and transport of waxy crude oil. However, few studies have dealt with the influence of paraffin molecular branching position on the gelling process. The focus of this study is to clarify the influence of branching distribution on molecular aggregation through molecular simulation, so as to further improve the mechanistic study of the gelling process of waxy crude oil. A variety of molecular models of crude oil systems containing paraffin molecules with different distributions of branched chains, asphaltenes, and light oils are developed to analyse the molecular aggregation and wax precipitation characteristics during the gelling process.The results show that the paraffin molecular chain morphology gradually from stretching to curling and the molecules gradually from dispersing to aggregating during the temperature drop process. From the van der Waals force analysis, it is concluded that isomeric alkanes with a close branching distribution form the weakest gelling structures. In addition, the phase transition temperature difference between n-alkanes and isoalkanes is large about 9 K, but the phase transition temperature difference between the two isoalkanes with different distributions of branched chains is small only about 3 K. This indicates that for alkanes with the same molecular formula, the length of the main carbon chain is a dominant factor in influencing the aggregation of the molecules and the gelling properties of the crude oil system. Under high temperature conditions, isomeric alkanes have the best mobility and are most sensitive to temperature. The results of the study can provide help for the mechanism of the gelling process of waxy crude oil to ensure the safety of the pipeline transmission process, and provide theoretical guidance for the production of depressants and catalysts.

Tail-approach based design, synthesis, and molecular modeling of benzenesulfonamides carrying thiadiazole and urea moieties as novel carbonic anhydrase inhibitors.

We synthesized herein 16 compounds (SUT1-SUT16) as potential carbonic anhydrase (CA) inhibitors utilizing the tail-approach design. Based on this strategy, we connected benzenesulfonamide, the zinc-binding scaffold, to different urea moieties with the 1,3,4-thiadiazole ring as a linker. We obtained the target compounds by the reaction of 4-(5-amino-1,3,4-thiadiazol-2-yl)benzenesulfonamide with aryl isocyanates. Upon confirmation of their structures, the compounds were screened for their ability to inhibit the tumor-related human (h) isoforms human carbonic anhydrase (hCA) IX and XII, as well as the physiologically dominant hCA I and II. Most of the molecules demonstrated Ki values ≤ 10 nM with different selectivity profiles. The binding modes of SUT9, SUT10, and SUT5, the most effective inhibitors of hCA II, IX, and XII, respectively, were predicted by molecular docking. SUT16 (4-{5-[3-(naphthalen-1-yl)ureido]-1,3,4-thiadiazol-2-yl}benzenesulfonamide) was found to be the most selective inhibitor of the cancer-associated isoforms hCA IX and XII over the off-target isoforms, hCAI and II. The interaction dynamics and stability of SUT16 within hCA IX and XII were investigated by molecular dynamics simulations as well as dynophore analysis. Based on computational data, increased hydrophobic contacts and hydrogen bonds in the tail part of these molecules within hCA IX and XII were found as favorable interactions leading to effective inhibitors of cancer-related isoforms.

Synthesis, structural analysis, and molecular docking of a novel 1,3,4-thiadiazole derivative: An experimental and molecular modeling studies

This study reports on the synthesis and characterization of a new thiadiazole derivative, (E)-N-(5-(2-nitrostyryl) -4-acetyl -4,5-dihydro -1,3,4-thiadiazol -2-yl) -N-phenylacetamide (ETDZ). The crystal structure was determined by single-crystal X-ray diffraction. ETDZ belongs to the monoclinic I2/a space group. The contribution of intermolecular interactions was assessed by Hirshfeld surface analysis and fingerprint plots. FT-IR, UV–Vis, and NMR (1H and 13C) techniques were used for spectroscopic characterization. The 1H and 13C NMR spectra were recorded in CDCl3 solvent. Density functional theory, employing the B3LYP functional and 6–311G(d,p) basis set in chloroform solvent, was used to calculate the structural and spectroscopic parameters of the molecule in the ground state. The vibrational wavenumbers were calculated and compared with the experimental FT-IR spectrum using the scaled quantum mechanics method. Isotropic chemical shifts were calculated using the Gauge invariant atomic orbital method. The calculated NMR chemical shifts and absorption wavelengths were compared with the experimental values, indicating good results from the DFT and TD-DFT methods. To get more information about charge transfer within the molecule, electronic properties such as HOMO and LUMO energies were studied using the DFT approach. The molecular electrostatic potential, frontier molecular orbital analysis, energy band gap, density of state, global chemical reactivity descriptors, and some thermodynamic functions were also calculated. Reduced density gradient and atom-in-molecule analysis were performed to investigate inter- and intra-non-covalent interactions. Molecular docking was carried out with the Eg5 kinesin protein, confirming the biological assets of the ETDZ ligand as a mitochondria disease and cancer agent.

Catalytic coal gasification: mechanism, kinetics, and reactor model

Catalytic coal gasification is a promising technology in the field of clean coal utilization. A comprehensive understanding of mechanisms, reaction kinetic, and reactor model is crucial. This article summarizes and analyzes the catalytic mechanisms of key reactions, such as C–O2, C–CO2, C–H2O, and CO–H2. It also compares various kinetic models, including shrinking core model, random pore model, volume model and their respective modifications. Additionally, the article delves into mathematical modellings of catalytic coal gasification, encompassing molecular models or density functional theory, empirical model, computational fluid dynamics, Aspen modeling, and artificial neural network. The aim is to provide a roadmap for the development and scale up of reactors used in catalytic coal gasification.