Dynamics Simulation Analysis Research Articles

Antifreeze Polysaccharides from Wheat Bran: The Structural Characterization and Antifreeze Mechanism.

Exploring a novel natural cryoprotectant and understanding its antifreeze mechanism allows the rational design of future sustainable antifreeze analogues. In this study, various antifreeze polysaccharides were isolated from wheat bran, and the antifreeze activity was comparatively studied in relation to the molecular structure. The antifreeze mechanism was further revealed based on the interactions of polysaccharides and water molecules through dynamic simulation analysis. The antifreeze polysaccharides showed distinct ice recrystallization inhibition activity, and structural analysis suggested that the polysaccharides were arabinoxylan, featuring a xylan backbone with a majority of Araf and minor fractions of Manp, Galp, and Glcp involved in the side chain. The antifreeze arabinoxylan, characterized by lower molecular weight, less branching, and more flexible conformation, could weaken the hydrogen bonding of the surrounding water molecules more evidently, thus retarding the transformation of water molecules into the ordered ice structure.

Research on Kinematics and Efficiency Calculation of Binary Logic Planetary Gearbox Based on Graph Theory

In this paper, the graph theory model of the kinematics of the double internal meshing planetary gear is established by splitting the k value of the planetary gear, the system matrix of the dual-state logic planetary gear transmission is assembled, the logic characteristics of the dual-state logic planetary gear transmission control are analyzed, the logic characteristic table of the 32-gear control is established, and the system model of the kinematics analysis and calculation of the entire planetary gear transmission is established. The expressions of rotational speed and transmission ratio of each component (including planetary gear) of the planetary gear in 32 gears are solved and obtained. The efficiency expression of each gear is derived through the Kleinas method, the calculation of the transmission ratio and efficiency of the 32 gears is completed, and the system efficiency diagram is drawn, which provides a reliable basis for the structural design, shift dynamic simulation analysis, and test verification of the dual-state logic planetary transmission.

Cracking a cancer code DNA methylation in epigenetic modification: an in-silico approach on efficacy assessment of Sri Lanka-oriented nutraceuticals

DNA methyltransferase (DNMTs) are essential epigenetic modifiers that play a critical role in gene regulation. These enzymes add a methyl group to cytosine’s 5'-carbon, specifically within CpG dinucleotides, using S-adenosyl-L-methionine. Abnormal overexpression of DNMTs can alter the gene expression patterns and contribute to cancer development in the human body. Therefore, the inhibition of DNMT is a promising therapeutic approach to cancer treatment. This study was aimed to identify potential nutraceutical inhibitors from the Sri Lanka Flora database using computational methods, which provided an atomic-level description of the drug binding site and examined the interactions between nutraceuticals and amino acids of the DNMT enzyme. A series of nutraceuticals from Sri Lanka-oriented plants were selected and evaluated to assess their inhibitory effects on DNMT using absorption, distribution, metabolism, excretion and toxicity analysis, virtual screening, molecular docking, molecular dynamics simulation and trajectory analysis. Azacitidine, a DNMT inhibitor approved by the US Food and Drug Administration, was selected as a reference inhibitor. The complexes with more negative binding energies were selected and further assessed for their potency. Seven molecules were identified from 200 nutraceuticals, demonstrating significantly negative binding energies against the DNMT enzyme. Various trajectory analyses were conducted to investigate the stability of the DNMT enzyme. The results indicated that petchicine (NP#0003), ouregidione (NP#0011) and azacitidine increased the stability of the DNMT enzyme. Consequently, these two nutraceuticals showed inhibitory efficacies similar to azacitidine, making them potential candidates for therapeutic interventions targeting DNMT enzyme-related cancers. Additional bioassay testing is recommended to confirm the efficacies of these nutraceuticals and explore their applicability in clinical treatments. Communicated by Ramaswamy H. Sarma

Inhibition of NS2B-NS3 protease from all four serotypes of dengue virus by punicalagin, punicalin and ellagic acid identified from Punica granatum

Despite a major threat to the public health in tropical and subtropical regions, dengue virus (DENV) infections are untreatable. Therefore, efforts are needed to investigate cost-effective therapeutic agents that could cure DENV infections in future. The NS2B-NS3 protease encoded by the genome of DENV is considered a critical target for the development of anti-dengue drugs. The objective of the current study was to find out a specific inhibitor of the NS2B-NS3 proteases from all four serotypes of DENV. To begin with, nine plant extracts with a medicinal history were evaluated for their role in inhibiting the NS2B-NS3 proteases by Fluorescence Resonance Energy Transfer (FRET) assay. Among the tested extracts, Punica granatum was found to be the most effective one. The metabolic profiling of this extract revealed the presence of several active compounds, including ellagic acid, punicalin and punicalagin, which are well-established antiviral agents. Further evaluation of IC50 values of these three antiviral molecules revealed punicalagin as the most potent anti-NS2B-NS3 protease drug with IC50 of 0.91 ± 0.10, 0.75 ± 0.05, 0.42 ± 0.03, 1.80 ± 0.16 µM against proteases from serotypes 1, 2, 3 and 4, respectively. The docking studies demonstrated that these compounds interacted at the active site of the enzyme, mainly with His and Ser residues. Molecular dynamics simulations analysis also showed the structural stability of the NS2B-NS3 proteases in the presence of punicalagin. In summary, this study concludes that the punicalagin can act as an effective inhibitor against NS2B-NS3 proteases from all four serotypes of DENV. Communicated by Ramaswamy H. Sarma

Designing surface exposed sites on Bacillus subtilis lipase A for spin-labeling and hydration studies

Spin-labeling with electron paramagnetic resonance spectroscopy (EPR) is a facile method for interrogating macromolecular flexibility, conformational changes, accessibility, and hydration. Within we present a computationally based approach for the rational selection of reporter sites in Bacillus subtilis lipase A (BSLA) for substitution to cysteine residues with subsequent modification with a spin-label that are expected to not significantly perturb the wild-type structure, dynamics, or enzymatic function. Experimental circular dichroism spectroscopy, Michaelis-Menten kinetic parameters and EPR spectroscopy data validate the success of this approach to computationally select reporter sites for future magnetic resonance investigations of hydration and hydration changes induced by polymer conjugation, tethering, immobilization, or amino acid substitution in BSLA. Analysis of molecular dynamic simulations of the impact of substitutions on the secondary structure agree well with experimental findings. We propose that this computationally guided approach for choosing spin-labeled EPR reporter sites, which evaluates relative surface accessibility coupled with hydrogen bonding occupancy of amino acids to the catalytic pocket via atomistic simulations, should be readily transferable to other macromolecular systems of interest including selecting sites for paramagnetic relaxation enhancement NMR studies, other spin-labeling EPR studies or any method requiring a tagging method where it is desirable to not alter enzyme stability or activity.

Pyruvate kinase deficiency and PKLR gene mutations: Insights from molecular dynamics simulation analysis

Pyruvate kinase deficiency is a rare hereditary erythrocyte enzyme disease caused by mutations in the pyruvate kinase liver and red blood cell gene. The clinical presentations of pyruvate kinase deficiency are significantly heterogeneous, ranging from just mild anemia to hemolytic crisis or even death. The proband in our study was a 2-year-old girl for severe skin and scleral icterus with progressive aggravation. We collected the family's data for further analysis. Whole exome genome sequencing of the pedigree revealed a novel compound heterozygous mutation, c.1097del (p.P366Lfs*12) and c.1493G > A (p.R498H), in the pyruvate kinase liver and red blood cell gene. Furthermore, molecular dynamics simulations were employed to uncover differences between the wild type and mutant pyruvate kinase liver and red blood cell proteins, focusing on structural stability, protein flexibility, secondary structure, and overall conformation. The combined bioinformatic tools were also utilised to assess the effects of the missense mutation on protein function. Thereafter, wild type and mutant plasmids were constructed and transfected into 293T cells, and Western blot assay was conducted to validate the impact of the mutations on the expression of pyruvate kinase liver and red blood cell protein. The data presented in our study enriches the genotype database and provides evidence for genetic counseling and molecular diagnosis of pyruvate kinase deficiency.

Biochemical and in silico analysis of the binding mode of erastin with tubulin

Erastin (ERN) is a small molecule that induces different forms of cell death. For example, it has been reported to induce ferroptosis by disrupting tubulin subunits that maintain the voltage-dependent anion channels (VDACs) of mitochondria. Although its possible binding to tubulin has been suggested, the fine details of the interaction between ERN and tubulin are poorly understood. Using a combination of biochemical, cell-model and in silico approaches, we elucidate the interactions of ERN with tubulin and their biological manifestations. After confirming ERN's antiproliferative efficacy (IC50, 20 ± 3.2 M) and induction of cell death in the breast cancer cell line MDA-MB-231, the binding interactions of ERN with tubulin were examined. ERN bound to tubulin in a concentration-dependent manner, disorganizing the structural integrity of the protein, as substantiated via the tryptophan-quenching assay and the aniline-naphthalene sulfonate binding assay, respectively. In silico studies based on molecular docking revealed a docking score of −5.863 kcal/mol, suggesting strong binding interactions of ERN with tubulin. Additionally, molecular dynamics simulation and Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) analyses evinced the binding free energy (ΔGbinding) of −31.235 kcal/mol, substantiating strong binding affinity of ERN with tubulin. Ligplot analysis showed hydrogen bonding with specific amino acids (Asn A226, Thr A223, Gln B247 and Val B355). QikProp-based ADME (absorption, distribution, metabolism and excretion) assessment showed considerable therapeutic potential for ERN. Communicated by Ramaswamy H. Sarma

Association of epilepsy and neurological impairments with homozygous recessive missense mutations found in the genes responsible for ganglioside biosynthesis (ST3GAL5) and calcium voltage-gated channels (CACNA1H) - insights through molecular dynamic simulations

With over 2.2 million cases, the incidence rate of epilepsy in Pakistan is far higher than the rest of the world due primarily to the frequent, traditionally imposed cousin marriages. In the present study, comprehensive whole exome sequencing (WES) analyses of a three-generation family with four affected members presenting ‘unexplained’ childhood absence epilepsy (CAE), seizures and dementia, was performed in a quest to identify heritable, epilepsy-causal gene variants to better aid in carrier screening and genetic counselling. The WES data was generated, analyzed, and validated through Sanger’s sequencing, molecular dynamic simulation (MDS) analysis, and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) studies. Two homozygous recessive, missense mutations in ST3GAL5 (c.311A > G, p. His104Arg) and CACNA1H (c.6230G > A, p. Arg2077His) genes, earlier regarded as benign or of uncertain significance, have been identified as a potential etiology. Comparative MDS and free binding energy calculations revealed substantial structural perturbations in mutant forms of ST3GAL5 leading to decreased binding and reduced catalytic activity of the p.His104Arg and two other functional variants (p.Val74Glu and p.Arg288Ter) when compared with wild type. Our findings reinforce that WES analyses may uncover ‘hidden’, heritable variants and together with MDS and MM/GBSA may provide plausible clues to answer the unexplained causes of epilepsy for an effective management and better patient outcome. Further, revisit of epilepsy-associated mutational landscape in population context is imperative as the variants with ‘benign’ tags may turn out to be ‘non-benign’, when exist in combination with other benign. Communicated by Ramaswamy H. Sarma

Identification of Novel EGFR Inhibitors for the Targeted Therapy of Colorectal Cancer Using Pharmacophore Modelling, Docking, Molecular Dynamic Simulation and Biological Activity Prediction.

Colorectal cancer (CRC) is considered the second deadliest cancer in the world. One of the reasons for the occurrence of this cancer is the deregulation of the Epidermal Growth Factor Receptor (EGFR), which plays a critical role in regulating cell division, persistence, differentiation, and migration. The overexpression of the EGFR protein leads to its dysregulation and causes CRC. Hence, this work aims to identify and validate novel EGFR inhibitors for the treatment of colorectal cancer employing various computer aided techniques such as pharmacophore modeling, docking, molecular dynamic simulation and Quantitative Structure-Activity Relationship (QSAR) analysis. In this work, a shared-featured ligand-based pharmacophore model was generated using the known inhibitors of EGFR. The best model was validated and screened against ZincPharmer and Maybridge databases, and 143 hits were obtained. Pharmacokinetic and toxicological properties of these hits were studied, and the acceptable ligands were docked against EGFR. The best five protein-ligand complexes with binding energy less than -5 kcal/mol were selected. The molecular dynamic simulation studies of these complexes were conducted for 100 nanoseconds (ns), and the results were analyzed. The biological activity of this ligand was calculated using QSAR analysis. The best complex with Root Mean Square Deviation (RMSD) 3.429 Å and Radius of Gyration (RoG) 20.181 Å was selected. The Root Mean Square Fluctuations (RMSF) results were also found to be satisfactory. The biological activity of this ligand was found to be 1.38 μM. This work hereby proposes the ligand 2-((1,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)oxy)-N- (1H-indol-4-yl)acetamide as a potential EGFR inhibitor for the treatment of colorectal cancer. The wet lab analysis must be conducted, however, to confirm this hypothesis.

On the transport behavior of shale gas in nanochannels with fractal roughness

As an efficient and environmentally friendly source of energy, shale gas is abundantly available and continues to contribute to the economy growth because of its huge potential for production. However, accurately predicting the transport behavior of shale gas is still challenging due to the small scale and complexity of nanochannels, which impedes the efficiency of recovery. In this paper, the transport behavior of shale gas in nanochannels with fractal roughness is studied by molecular dynamics simulation and theoretical analysis. It is found that the present work functions well to predict the transport behavior of shale gas in nanochannels with roughness. The introduction of fractal roughness hinders the transport of shale gas and leads to a complex trajectory of methane molecules in nanochannels. Furthermore, it is interesting to find the average gas viscosity increases, while the gas flux decreases with the increase in the inclined angle due to the impediment effect after the deflection. These results are helpful for understanding the migration of shale gas in nanochannels with roughness and guiding the improvement of shale gas recovery in practical applications.

Evaluation of novel Anti-SARS-CoV-2 compounds by targeting nucleoprotein and envelope protein through homology modeling, docking simulations, ADMET, and molecular dynamic simulations with the MM/GBSA calculation

The current prominent virus that induces severe acute respiratory syndrome is SARS-CoV-2. The incidence of COVID-19 cases is increasing, necessitating the immediate development of effective treatments. Our objective was to employ an in-silico approach to evaluate the effectiveness of conventional compounds against COVID-19's nucleoprotein and envelope protein. A docking simulation was performed on 9 compounds as SARS-coronavirus inhibitors using AMDock software. Anti-covid-19 activities were further evaluated for the compounds. Based on docking results, the binding affinity of "N-(4-carbamoylphenyl)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxamide,” also called compound 36 in this research, was found to be −8.8 ​kcal/mol for the modeled envelope protein and −7.3 ​kcal/mol for the template envelope protein, while −10.1 ​kcal/mol for the modeled nucleocapsid proteins (NP) and −8.7 ​kcal/mol for the template nucleocapsid proteins (NP) of SARS-coronavirus, respectively. The ligand and control drug (ritonavir) with high docking scores were subjected to pharmacological screening, molecular dynamic simulations, and Molecular Mechanics-generalized Born Surface Area (MM/GBSA) calculations. Furthermore, the jobs of pharmacokinetics were assessed, and the outcomes acquired show that the proposed compound 36 includes great oral bioavailability and a capacity to diffuse through various organic boundaries. The protein-ligand complexes were subjected to dynamic simulation analyses with a re-enactment time of 10 ns, likewise, their free binding energy was inspected operating the MM/GBSA approach. The docking (MD simulation) results acquired emphasize the pivotal residues answerable for the protein-ligand interaction, giving an understanding of the method of association. The MD simulation analysis verifies the structural stability of the selected complexes during the MD trajectory, with minor changes detected. The MM/GBSA data show that compound 36 has the lowest free energy of −12.498 ​kcal/mol for EP and −57.5185 ​kcal/mol for NP proteins of SARS-coronavirus, confirming the molecular docking result. As a result, the identified chemical can be used to develop a new family of antiviral medications against SARS-coronavirus-2.

Optimizing and designing upper-stage separation spring of lifting-body rocket

Because the upper-stage separation of a lifting-body rocket is difficult under the low-altitude and high-speed flight environments, an upper-stage separation scheme based on the separation spring is proposed. The integration of ADAMS and MATLAB realizes the multi-body dynamics simulation analysis of upper-stage separation. The experimental design method is used to carry out the target simulation and calculation of the upper-stage separation process, with the separation condition deviation and the separation spring deviation considered at the same time, thus ensuring the reliability of the separation scheme. In order to further optimize the separation scheme, an upper-stage separation optimization model is established with the Isight software, and the mass of separation spring is optimized with the multi-island genetic algorithm and significantly reduced by 48.87% under the condition that the upper-stage separation process satisfies all constraints, thereby effectively improving the performance of the lifting-body rocket.

Dynamic simulation analysis of molten salt reactor-coupled air–steam combined cycle power generation system

Dynamic simulation analysis of molten salt reactor-coupled air–steam combined cycle power generation system

Molecular dynamics simulation analysis of the effects and mechanisms of lipid nanoparticles in drug delivery systems

Molecular dynamics simulation analysis of the effects and mechanisms of lipid nanoparticles in drug delivery systems

Percolating Network of Anionic Vacancies in Prussian Blue: Origin of Superior Ammonium-Ion Storage Performance.

Emerging aqueous ammonium-ion batteries (AIBs) are considered inexpensive, highly safe, ecofriendly, and sustainable energy storage systems. Although some high-performance electrode materials have been reported for AIBs, a comprehensive understanding of the origin of the high ammonium-ion storage performance is still lacking. Herein, the percolating network of anionic vacancies is determined to be the origin of the superior ammonium-ion storage properties of the Prussian blue analogues based on ab initio molecular dynamics simulation and electrochemical kinetic analyses. Fe[Fe(CN)6] with a percolating anionic vacancy network delivers an outstanding rate of 64.7 mAh g-1 at 2000 mA g-1 in addition to a capacity retention of 94.5% after 10 000 cycles. The low-strain intercalation ammonium-ion storage mechanism of highly deficient Fe Prussian blue with Fe as the redox center is revealed by in situ X-ray diffraction and ex situ X-ray absorption fine structure analysis. The results provide insights into the mechanism of ammonium-ion storage in Prussian blue analogues and guidance in the development of aqueous AIBs.

Discovery of thiazolidinedione-based pancreatic lipase inhibitors as anti-obesity agents: synthesis, in silico studies and pharmacological investigations

A series of new 2,5-disubstituted arylidene derivatives of thiazolidinedione (16a-e, 17a-d, 18a-c) designed using molecular hybridization approach were synthesized, structurally characterized, and explored for their anti-obesity potential via inhibition of Pancreatic Lipase (PL). Compound 18a presented the most potent PL inhibitory activity with IC50 = 2.71 ± 0.31 µM, as compared to the standard drug, Orlistat (IC50 = 0.99 µM). Kinetic study revealed reversible competitive mode of enzyme inhibition by compound 18a with an inhibitory constant value of 1.19 µM. The most promising compound 18a revealed satisfactory binding mode within the active site of the target protein (human PL, PDB ID: 1LPB). Also, MM/PBSA binding free energy and molecular dynamics (MD) simulation analysis were performed for the most promising compound 18a, which showed potent inhibition according to the results of in vitro studies. Furthermore, a stable conformation of the 1LPB-ligand suggested the stability of this compound in the dynamic environment. The ADME and toxicity analysis of the compounds were examined using web-based online platforms. Results of in vivo studies confirmed the anti-obesity efficacy of compound 18a, wherein oral treatment with compound 18a (30 mg/kg) resulted in a significant reduction in the body weight, BMI, Lee index, feed intake (in Kcal), body fat depots and serum triglycerides. Compound 18a significantly decreased the levels of serum total cholesterol (TC) to 128.6 ± 0.59 mg/dl and serum total triglycerides (TG) to 95.73 ± 0.67 mg/dl as compared to the HFD control group. The present study identified disubstituted TZD derivatives as a new promising class of anti-obesity agents. Communicated by Ramaswamy H. Sarma

Retracted: Dynamic Modeling and Simulation Analysis of Virtual Product Design and Creation Based on OSG Artificial Intelligence Platform

Retracted: Dynamic Modeling and Simulation Analysis of Virtual Product Design and Creation Based on OSG Artificial Intelligence Platform

The in vitro and in vivo antiviral effects of IGF1R inhibitors against respiratory syncytial virus infection

The insulin-like growth factor 1 receptor (IGF1R) was recognized as a pivotal receptor that facilitated the cellular entry of RSV. Small molecule inhibitors designed to target IGF1R exhibited potential as potent antiviral agents. Through virtual screening, we conducted a screening process involving small molecule compounds derived from natural products, aiming to target the IGF1R protein against respiratory syncytial virus infection. The molecular dynamics simulation analysis showed that tannic acid and daptomycin interacted with the IGF1R. The experimental results in vivo and in vitro showed that tannic acid and daptomycin had anti-RSV infection potential through reducing viral loads, inflammation, airway resistance and protecting alveolar integrity. The CC50 values of tannic acid and daptomycin were 6 nM and 0.45 μM, respectively. Novel small-molecule inhibitors targeting the IGF1R, tannic acid and daptomycin, may be effective anti-RSV therapy agents. This study may in future broaden the arsenal of therapeutics for use against RSV infection and lead to more effective care against the virus. Communicated by Ramaswamy H. Sarma

Inhibiting the oligomerization of mycobacterial DNA-directed RNA polymerase (RNAP) using natural compound via in-silico techniques

Mycobacterium tuberculosis (Mtb) is responsible for the spread of tuberculosis (TB). The current study employed virtual screening of 2569 natural compounds against the DNA-directed RNA polymerase (RNAP) of Mtb to identify the possible binders that can inhibit its function. The in-silico methodology included molecular docking to the compounds, further, the stability and flexibility of the best complexes were studied using molecular dynamics simulation, the MM/GBSA binding free energy technique with energy decomposition, PCA, FEL, steered MD simulation, and umbrella sampling. Individual virtual screenings were conducted for the five RNAP subunits (chains A, B, C, D, and E) to identify a compound capable of inhibiting RNAP oligomerization. A promising compound, isoestradiol 3-benzoate, exhibited a low binding score (−7.28 ​kcal/mol to −8.21 ​kcal/mol) and showed binding ability with all subunits of the protein. Thus, the five complexes with isoestradiol 3-benzoate were selected for molecular dynamics simulation analysis. Furthermore, RMSD showed that isoestradiol 3-benzoate bound with chain E showed the lowest RMSD of 0.49 ​nm, while with chains A and B it had the most stable and consistent conformations with RMSD of 1.75 ​nm and 1.2 ​nm, respectively. The H-bond between isoestradiol 3-benzoate and chains C and E showed the highest occupancy (58.27 ​%, 45.33 ​%, and 50.80 ​%, 42.25 ​%, 11.75 ​%). Moreover, the MMPBSA technique showed that isoestradiol 3-benzoate had a strong association with chains B and C (ΔGbind ​= ​−126.25 ​± ​2.03 and −129.27 ​± ​2.25). Additionally, free energy decomposition, PCA, FEL-steered MD simulation, and umbrella sampling were also performed to validate the association of the ligand with the protein. Isoestradiol 3-benzoate binds strongly to chains B and E; therefore, it should be considered as viable candidate for inhibiting the formation of RNAP protein complex, concluded in this study.

Ursolic acid acetate and iso-mukaadial acetate bind to Plasmodium falciparum Hsp90, abrogating its chaperone function in vitro

Plasmodium falciparum is the most lethal malaria parasite. Increasing incidences of drug resistance of P. falciparum have prompted the need for discovering new and effective antimalarial compounds with an alternative mode of action. Heat shock protein 90 (PfHsp90) facilitates protein folding and is a promising antimalarial drug target. We have previously reported that iso-mukaadial acetate (IMA) and ursolic acid acetate (UAA) exhibit antimalarial activity. We investigated the abilities of IMA and UAA to bind PfHsp90 by molecular docking and dynamics simulations. The in silico predictions were validated by biochemical assays conducted on recombinant PfHsp90. The interaction between the ligands and PfHsp90 was evaluated using ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FTIR), and surface plasmon resonance (SPR) analysis. The results obtained by docking calculations and MD dynamics simulation predicted that UAA and IMA preferentially bound to PfHsp90 via the N-terminal domain, with UAA binding more stable than IMA. UV-vis-based data suggest that PfHsp90 harbors buried aromatic amino acids, which were exposed in the presence of either IMA or UAA. In addition, data obtained using FTIR suggested that IMA and UAA destabilized the secondary structure of PfHsp90. Of the two compounds, UAA bound to PfHsp90 within the micromolar range based on surface plasmon resonance (SPR)-based binding assay. Furthermore, both compounds disrupted the holdase chaperone function of PfHsp90 as the chaperone failed to suppress heat-induced aggregation of the model proteins, malate dehydrogenase (MDH), luciferase, and citrate synthase in vitro. In addition, both compounds lowered the ATPase activity of PfHsp90. The molecular dynamics simulation analysis indicated that the docked complexes were mostly stable for 100 ns, validating the data obtained through the biochemical assays. Altogether, this study expands the repository of antiplasmodial compounds that have PfHsp90 among their possible targets.