Molecular Dynamics Study Research Articles

Development of Fragment-Based Inhibitors of the Bacterial Deacetylase LpxC with Low Nanomolar Activity.

In a fragment-based approach using NMR spectroscopy, benzyloxyacetohydroxamic acid-derived inhibitors of the bacterial deacetylase LpxC bearing a substituent to target the uridine diphosphate-binding site of the enzyme were developed. By appending privileged fragments via a suitable linker, potent LpxC inhibitors with promising antibacterial activities could be obtained, like the one-digit nanomolar LpxC inhibitor (S)-13j [Ki (EcLpxC C63A) = 9.5 nM; Ki (PaLpxC): 5.6 nM]. To rationalize the observed structure-activity relationships, molecular docking and molecular dynamics studies were performed. Initial in vitro absorption-distribution-metabolism-excretion-toxicity (ADMET) studies of the most potent compounds have paved the way for multiparameter optimization of our newly developed isoserine-based amides.

Kinetic insight of multi-molecule adsorption behaviors into the anticorrosion performance of azole inhibitors: A reactive force field molecular dynamics study

Density functional theory (DFT) calculations and molecular dynamics (MD) simulations are established as powerful tools in understanding the anti-corrosion mechanism of inhibitors at the atomic scale. Despite their widespread popularity, DFT calculations typically focus on small adsorption models while the inhibition efficiency of inhibitors is determined by multi-molecule adsorption film on metal surface. Classical MD simulations neglect the formation of chemical bonding, which frequently governs the overall adsorption process. In this contribution, reactive force field (ReaxFF) MD simulations were employed to overcome these limitations and investigate the differences in inhibitory capabilities among three classic azole compounds: imidazole (IDZ), 1,2,4-triazole (TAZ), and benzotriazole (BTA) on copper. Electrochemical tests and microscopic observations revealed that BTA demonstrated superior inhibitory effect on copper corrosion compared to IDZ and TAZ. However, the widely used descriptor, adsorption energy (Eads) in DFT calculations for predicting the inhibition ability of inhibitors were very similar, failing to explain the enormous variation in inhibition effectiveness. To explain this disparity, multi-molecule adsorption kinetics based on ReaxFF simulations were conducted. The results showed that BTA consistently demonstrated faster and more frequent adsorption on copper surface compared to the other two. The significant variance in inhibitory efficiency among the three inhibitors was elucidated for the first time from the kinetic insight.

Molecular dynamics study on structural characteristics of amorphous C‐S‐H with different Ca/Si ratios

AbstractAs the major hydration product of cement, hydrated calcium silicate (C‐S‐H) governs the overall performance of cement‐based materials. The molar ratio of CaO to SiO2 (Ca/Si ratio) significantly affects the structure and properties of C‐S‐H. This study analyzed the effect of Ca/Si ratios (0.83–2.0) on the structural morphology evolution, bond lengths and angles, polymerization process, and nanoporosity of amorphous C‐S‐H, with the help of the ReaxFF force field. The results showed that the reacted C‐S‐H tend to form a fibrous network‐like morphology at low Ca/Si ratios, while the silicate chains are prone to accumulating at high Ca/Si ratios, forming a dense granular ovoid structure. Meanwhile, the Ca/Si ratio has no effect on the bond lengths and angles. In addition, the Ca2+ ions can interrupt the silicate chains during hydration, which leads to a decrease in the average silicate chain length with increasing Ca/Si ratio. The porosity of C‐S‐H decreases from 59.3% to 54.3% when the Ca/Si ratio increases from 0.83 to 2.0. It can be deduced from these findings that the increase in the Ca/Si ratio decreases the compressive strength of cement‐based materials but increases their durability.

Effect of grain boundaries on the helium degradation mechanisms of alloy 800H: A molecular dynamics study

Alloy 800H is currently used as structural material in light-water cooled nuclear reactors, and it is also considered as candidate materials for various advanced reactor designs. Under operation, the exposure of alloy 800H to neutron irradiation results in the formation of helium (He), mainly from Ni by the transmutation reaction (n, α). In this work, we present a molecular dynamics (MD) simulation study of the behavior and effects of He on the microstructure and mechanical properties of alloy 800H. Our results show that the population of clusters made of 5 to 9 He atoms is nearly constant throughout the simulation time (10 ns), while the population of larger clusters increases as the simulation time increases. The growth of clusters is controlled by either the dissociation and diffusion of smaller clusters towards nearby larger clusters or the merging of larger clusters initially located nearby to each other. A significant accumulation of He is observed at the grain boundaries (GB), while a depletion zone is found at the neighboring regions. As a result, the density of He cluster is significantly higher at the GBs as compared to the intra-granular regions. The nucleation and growth of He clusters also results in the formation of Frenkel pairs (FP), whose associated self-interstitial atoms (SIA) agglomerate into interstitial clusters in the alloy 800H matrix. As a consequence, dislocation segments, mostly of the Shockley type, are generated in the microstructure, and often located next to He clusters. The combination of the aforementioned defect structures and the high density of He clusters at the GBs results in a substantial degradation of the mechanical properties of alloy 800H single crystal and bicrystals.

Study on the Inhibitory Effect of Bioactive Peptides Derived from Yak Milk Cheese on Cholesterol Esterase.

The bioactive peptides derived from yak milk cheese exhibited cholesterol-lowering properties. However, there was limited research on their inhibitory effects on cholesterol esterase (CE) and elucidation of their potential inhibitory mechanisms. In this study, we identified CE-inhibiting peptides through virtual screening and in vitro assays. Additionally, molecular docking and molecular dynamics studies were conducted to explore the mechanisms. The results indicated that peptides RK7 (RPKHPIK), KQ7 (KVLPVPQ), QP13 (QEPVLGPVRGPFP), TL9 (TPVVVPPFL), VN10 (VYPFPGPIPN), LQ10 (LPPTVMFPPQ), and SN12 (SLVYPFPGPIPN) possessed molecular weights of less than 1.5 kDa and a high proportion of hydrophobic amino acids, demonstrating notable inhibitory effects on CE. Molecular docking and dynamics revealed that peptides RK7, KQ7, QP13, and VN10 bound to key amino acid residues Arg423, His435, and Ser422 of CE through hydrogen bonds, hydrophobic interactions, salt bridges, and π-π stacking, occupying the substrate-binding site and exerting inhibitory effects on CE. The four peptides were further synthesized to verify their CE-inhibitory effects in vitro. RK7, KQ7, QP13, and VN10 exhibited inhibitory activity on CE with IC50 values of 8.16 × 10-7 mol/L, 8.10 × 10-7 mol/L, 4.63 × 10-7 mol/L, and 7.97 × 10-7 mol/L; RK7, KQ7, QP13, and VN10 were effective in inhibiting CE after simulated gastrointestinal digestion, especially with a significant increase in the inhibitory activity of KQ7 and RK7, respectively. Our findings suggested that bioactive peptides from yak milk cheese represented a novel class of potential CE inhibitors.

Novel quinoline-4-carboxamide derivatives potentiates apoptosis by targeting PDK1 to overcome chemo-resistance in colorectal cancer: Theoretical and experimental results

A series of novel N,2-diphenyl-6-(aryl/heteroaryl)quinoline-4-carboxamide derivatives were designed and synthesized using the Suzuki coupling reaction and evaluated them for their anticancer activity. These compounds were screened for anti-colon cancer activity through in-silico studies by molecular docking and molecular dynamics studies. Furthermore, the density functional theory was used to determine the molecule's electrical properties. The molecular electrostatic potential map is used to evaluate the charge distribution on the molecule surface. Unveiling that the compound 7a (binding energy of −10.2 kcal/mol) has good inhibition activity compared to other synthesized compounds (7b-7j) as well as the standard drug Gefitinib. The stability of the compound 7a with the 1OKY protein was confirmed through molecular dynamics simulation studies, indicating potential anti-colon cancer activity against phosphoinositide dependent protein kinase-1 (PDK1). The in-silico ADMET pharmacokinetic properties indicate adherence to Lipinski's rule of five for favorable safety profiles and the compound falls within the optimal range for physicochemical and pharmacokinetic properties, which is comparable to that of the standard medication drug Gefitinib. The synthesized library of compounds was further evaluated for their in-vitro anticancer potency against colon, pancreatic and breast cancer cells. The results demonstrated that the compounds effectively suppressed the proliferative potential of the screened cells in a concentration-dependent manner, as revealed by MTT assay. The anticancer potential of these molecules was further evaluated by acridine orange/PI, and Hoechst/PI which demonstrates the potential of molecules to induce apoptosis in cancer cells. Further investigations and optimization of these derivatives could lead to the development of effective anticancer strategies.

Moisture damage mechanism of asphalt mixtures containing reclaimed asphalt pavement binder: A novel molecular dynamics study

Reclaimed asphalt pavement (RAP) stands at the forefront of sustainable practices in road construction and rehabilitation. However, concerns regarding the moisture susceptibility of aged RAP binder have arisen due to its potential hazard to pavement durability. So far, the underlying mechanisms of how moisture infiltrates into the mixture and results in binder stripping remain controversial and scarcely investigated. To address this challenge, a novel molecular dynamics (MD) simulation method has been developed to explore the nanoscale stripping mechanisms, considering the effects of asphalt oxidative aging and rejuvenation. The results indicate that hydrogen bonding interactions between water and the aggregate surface reduce the contact distance compared to the distance between asphalt and aggregate. Under pore water pressure, moisture diffuses into the interface, occupying the van der Waals adhesion sites of asphalt molecules and consequently causing detachment. Asphalt oxidative aging, on one hand, increases the oxygen concentration and hydrophilicity, thereby increasing moisture susceptibility from the energy perspective. On the other hand, it increases the intermolecular friction between aged asphalt molecules, leading to reduced flexibility and age hardening, consequently triggering asphalt premature detachment and diminishing its coating quality on the aggregate surface. Rejuvenators can restore the moisture sensitivity of severely aged asphalt, with a mechanism involving two aspects: firstly, reducing the agglomeration and proportion of polar components in asphalt, thereby weakening its hydrophilicity; secondly, lubricating aged asphalt molecules to restore their flexibility and surface coating properties. Findings from this study contribute to revealing the moisture-induced damage mechanism when recycling RAP binder.

Exploration of Tertiary Structure in Sequence-Defined Polymers Using Molecular Dynamics Simulations.

Peptoids are a class of sequence-defined biomimetic polymers with peptide-like backbones and side chains located on backbone nitrogens rather than alpha carbons. These materials demonstrate a strong ability for precise control of single-chain structure, multiunit self-assembly, and macromolecular assembly through careful tuning of sequence due to the diversity of available side chains, although the driving forces behind these assemblies are often not understood. Prior experimental work has shown that linked 15mer peptoids can mimic the protein helical hairpin structure by leveraging the chirality-inducing nature of bulky side chains and hydrophobicity, but there are still gaps in our understanding of the relationship between sequence, stability, and particular secondary or tertiary structure. We present a molecular dynamics (MD) study on the folding behavior of these polymers into hairpins, discussing the differences in structure from sequences with various characteristics in water and acetonitrile, and then compare the handedness preference of common helical motifs between solvents.

Synthesis, Characterization, and In vitro and In Silico Studies of New Triazole Derivatives as Aromatase Inhibitors

Introduction: Breast cancer is the most common type of cancer among women. Steroidal or non-steroidal aromatase inhibitors (NSAIs) are used clinically, and in most cancer diseases, resistance is the most important problem. Method: The nitrogenous heterocyclic ring is noteworthy in the structure of non-steroidal aromatase inhibitors. This is the pharmacophore structure for aromatase inhibition. Because the enzyme interacts with the Fe2+ cation of the HEM structure in its active site, the most used agents in the clinic, such as anastrozole and letrozole, contain triazoles in their structures. Within the scope of this study, hybrid compounds containing both imidazole and triazole were synthesized. Result: The synthesis was carried out by a 4-step reaction. The anticancer effects of the compounds were evaluated by MTT assay performed on A549 and MCF-7 cancer cells. Compound 4d showed anticancer activity against the MCF-7 cell line with IC50=6.7342 uM value. This compound exhibited anticancer activity against the A549 cell line with an IC50 = 17.1761 μM. In the MTT test performed on a healthy cell line to determine the cytotoxic effects of the compounds, the compound showed activity with a value of 4d IC50=13.2088 uM. This indicates that the compound is not cytotoxic. Additionally, BrdU analysis was performed to evaluate whether the compound inhibits DNA synthesis. These selective effects of the compounds on breast cancer strengthened their aromatase enzyme inhibitor potential. For this reason, experiments conducted with both in vitro and in silico methods revealed a compound with high aromatase inhibitor potential. Conclusion: The interactions observed as a result of molecular docking and dynamics studies are in harmony with activity studies. In particular, interactions with HEM600 demonstrate the activity potential of the compound.

Exploring Chemical Space to Identify Partial Binders Against hMPV Nucleocapsid Protein.

Human metapneumovirus (hMPV) has gained prominence in recent times as the predominant etiological agent of acute respiratory tract infections. This virus targets children, the elderly, and individuals with compromised immune systems. Given the protracted duration of hMPV transmission, it is probable that the majority of children will have acquired the virus by the age of 5. In individuals with compromised immune systems, recurrence of hMPV infection is possible. As hMPV matures, it remains latent from the time of acquisition. The genome of hMPV encompasses a pivotal protein referred to as the nucleocapsid protein (N). This protein assumes the form of a left-handed helical nucleocapsid, enveloping the viral RNA genome. The primary function of this structure is to protect nucleases, rendering it a potentially promising target for therapeutic advancements. The present study employs a methodology that involves structure-based virtual screening, followed by molecular dynamics simulation at a 250-ns time scale, to identify potential natural molecules or their derivatives from the ZINC Database. These molecules are investigated for their binding properties against the hMPV nucleoprotein. Based on an evaluation of the docking score, binding site interaction, and molecular dynamics studies, it has been found that two naturally occurring molecules, namely M1 (ZINC85629735) and M3 (ZINC85569125), have shown notable docking scores of -9.6and -10.7 kcal/mol, acceptable RMSD, RMSF, Rg, and soon calculated from molecular dynamics trajectory associated with MMGBSA binding energy of -81.94 and -99.63 kcal/mol, respectively. These molecules have shown the highest binding affinity towardnucleocapsid protein and demonstrated promising attributes as potential binders against hMPV.

A molecular dynamics study of the effects of silane and cellulose nanocrystals at a glass fiber and epoxy interphase

A molecular dynamics study of the effects of silane and cellulose nanocrystals at a glass fiber and epoxy interphase

Advancing Optoglycomics: Two Orthogonal Azobenzene Glycoside Antennas in One Glycocluster-Synthesis, Switching Cycles, Kinetics and Molecular Dynamics.

Carbohydrate recognition is essential for numerous biological processes and is governed by various factors within the supramolecular environment of the cell. Photoswitchable glycoconjugates have proven as valuable tools for the investigation and modulation of carbohydrate recognition as they allow to control the relative orientation of sugar ligands by light. In order to advance the possibilities of such an "optoglycomics" approach for the glycosciences, we have synthesized a biantennary glycocluster in which two glycoazobenzene antennas are conjugated to the 3- and 6-position of a scaffold glycoside. Orthogonal isomerization of the photoswitchable units was made possible by the different conjugation of the azobenzene moieties via an oxygen and a sulfur atom, respectively, and the ortho-fluorination of one of the azobenzene units. This design enabled a switching cycle comprising the EE, EZ and the ZZ isomer. This is the first example of an orthogonally photoswitchable glycocluster. The full analysis of its photochromic properties included the investigation of the isolated glycoazobenzene antennas allowing the comparison of the intra- versus the intermolecular orthogonal photoswitching. The kinetics of the thermal relaxation were analyzed in detail. A molecular dynamics study shows that indeed, the relative orientation of the glycoantennas and the distances between the terminal sugar ligands significantly vary depending on the isomeric state, as intended.

Design of a novel EmTSP-3 and EmTIP based multi-epitope vaccine against Echinococcus multilocularis infection.

Current treatments and prevention strategies for echinococcosis are inadequate. Recent advancements in molecular vaccine development show promise against Echinococcus granulosus; however, Echinococcus multilocularis remains a challenge. A Multi-epitope Vaccine could potentially induce specific B and T lymphocyte responses, thereby offering protection against Echinococcus multilocularis infection. This study aimed to develop a MEV against alveolar echinococcosis. Key epitopes from the Echinococcus multilocularis proteins EmTSP3 and EmTIP were identified using immunoinformatics analyses. These analyses were conducted to assess the MEV feasibility, structural characteristics, molecular docking, molecular dynamics simulations, and immune simulations. The immunogenicity and antigenicity of the vaccine were evaluated through in vitro and in vivo experiments, employing ELISA, Western blotting, FCM, challenge infection experiments, and ELISPOT. The effective antigenicity and immunogenicity of MEV were demonstrated through immunoinformatics, as well as in vitro and in vivo experiments. In vitro experiments revealed that MEV increased the secretion of IFN-γ and IL-4 in PBMC and successfully bound to specific antibodies in patient serum. Furthermore, mice immunized with MEV developed a robust immune response, characterized by elevated levels of CD4+ and CD8+ T-cells, increased secretion of IFN-γ and IL-4 by specific Th1 and Th2 cells, and heightened serum antibody levels. Importantly, MEV reduced the weight of cysts by conferring resistance against echinococcosis. These findings suggest that MEV is a promising candidate for the prevention of Echinococcus multilocularis infection. A total of 7 CTL, 7 HTL, 5 linear B-cell, and 2 conformational B-cell epitopes were identified. The vaccine has demonstrated effective antigenicity and immunogenicity against AE through molecular docking, immune simulation, molecular dynamics studies, and both in vitro and in vivo experiments. It provides effective protection against Echinococcus multilocularis infection, thereby laying a foundation for further development.

Electronic excitation-induced amorphization in GaN and β-Ga2O3: an ab initio molecular dynamics study

Electronic excitation-induced amorphization in GaN and β-Ga2O3: an ab initio molecular dynamics study

Molecular dynamics study of the mechanism of explosive boiling on hybrid wettability surfaces

In this work, molecular dynamics (MD) simulation is applied to study the effect of heating surfaces with different hydrophobicity occupancy ratios (the ratio of the surface area of hydrophobic spots to the total area of the heating surface) on the boiling process of the liquid film explosion. At the same time, the mechanism is revealed from the trajectory of argon atoms. The simulation results showed that the onset of explosive boiling was later for purely hydrophilic surfaces than for hybrid wettability surfaces with a hydrophobicity percentage of <11%. The earliest onset of explosive boiling was observed for the heated surfaces with a hydrophobicity ratio of 6%. In addition, it was found that the superheat required for explosive boiling tended to decrease first and then increase with the gradual increase of the hydrophobicity ratio. Hydrophobic spots arranged on the surface provided bubble nucleation earlier for explosive boiling while enhancing convective heat transfer and thermal perturbation. The critical heat flux (CHF) of the heated surfaces with a hydrophobicity ratio of <11% were all greater than that of the purely hydrophilic surfaces, and all reached the CHF before the purely hydrophilic surfaces.

Structural transitions in liquid semiconductor alloys: A molecular dynamics study with a neural network potential.

Liquid-liquid phase transitions hold a unique and profound significance within condensed matter physics. These transitions, while conceptually intriguing, often pose formidable computational challenges. However, recent advances in neural network (NN) potentials offer a promising avenue to effectively address these challenges. In this paper, we delve into the structural transitions of liquid CdTe, CdS, and their alloy systems using molecular dynamics simulations, harnessing the power of an NN potential named LaspNN. Our investigations encompass both pressure and temperature effects. Through our simulations, we uncover three primary liquid structures around melting points that emerge as pressure increases: tetrahedral, rock salt, and close-packed structures, which greatly resemble those of solid states. In the high-temperature regime, we observe the formation of Te chains and S dimers, providing a deeper understanding of the liquid's atomic arrangements. When examining CdSxTe1-x alloys, our findings indicate that a small substitution of S by Te atoms for S-rich alloys (x > 0.5) exhibits a structural transition much different from CdS, while a large substitution of Te by S atoms for Te-rich alloys (x < 0.5) barely exhibits a structural transition similar to CdTe. We construct a schematic diagram for liquid alloys that considers both temperature and pressure, providing a comprehensive overview of the alloy system's behavior. The local aggregation of Te atoms demonstrates a linear relationship with alloy composition x, whereas that of S atoms exhibits a nonlinear one, shedding light on the composition-dependent structural changes.

Toughening Mechanism in Nanotwinned Boron Carbide: A Molecular Dynamics Study.

Boron carbide ceramics are potentially ideal candidates for lightweight bulletproof armor, but their use is currently limited by their low fracture toughness. Recent experimental results have shown that sintered samples with high twin densities exhibit high fracture toughness, but the toughening mechanism and associated crack propagation process of nanotwinned boron carbide at the atomic scale remain a mystery. Reported here are molecular dynamics simulations with a reactive force field potential to investigate how nanoscale twins affect the fracture toughness of boron carbide ceramics. The results show that the strength disparity on either side of a twin boundary is the fundamental reason for the toughening effect; the twin boundary impedes crack propagation only when the crack moves to a region of higher fracture strength. The fracture toughness of nanotwinned boron carbide is greatly affected by the angle between the twin boundary and the prefabricated crack. At an angle of 120°, the twin boundary provides the maximum toughening effect, enhancing the toughness by 32.72%. Moreover, phase boundaries-another common structure in boron carbide ceramics-have no toughening effect. This study provides new insights into the design of boron carbide ceramics with high fracture toughness.

Structural insights into polyethylene terephthalate (PET)-degrading archaeal lipase enzyme: An insilico approach

Biodegradation of plastic is the most eco-friendly degradation process conferred by various microbial enzymes, especially the lipase enzymes. The lipase enzymes depict a broad substrate range, high regio/stereoselectivity, and stability in organic solvents. However, enhancing the catalytic activity of lipases for industrial production remains a challenge, predominantly due to the need for their extensive mechanistic characterization. Here, we employed a multidisciplinary approach to illustrate the comprehensive physiochemical and mechanical properties of 102 lipase sequences from six different groups of plastic-degrading microorganisms. Molecular docking-based evaluation of the binding efficiencies of selected lipases with the most common plastic polymers- polyurethane (PUR) and polyethylene terephthalate (PET), revealed that the archaeal lipase had the lowest binding energy of −7.1 kcal/mol with PET. Remarkably, the molecular dynamic simulation studies (up to 100 ns) and very low RMSD (0.3 nm) and RMSF (0.25 nm) values further ascertained the stability of archaeal lipase after binding with PET polymer. Further, a 2.19 nm radius of gyration (Rg) within 100 ns simulation time, binding free energy ΔGTOTAL with −24.36 kcal/mol and entropy factor -TΔS 7.65 kcal/mol also indicated strong binding of archaeal lipase with PET polymer. The mechanistic exploration of archaeal lipase yielded valuable insights into its effective binding with PET polymer, paving the way for future lipase enzyme engineering and harnessing its industrial potential for plastic biodegradation.

Molecular hybridization assisted multi-technique approach for designing USP21 inhibitors to halt catalytic triad-mediated nucleophilic attack and suppress pancreatic ductal adenocarcinoma progression: A molecular dynamics study

AimsPancreatic cancer, the 12th-most common cancer, globally, is highly challenging to treat due to its complex epigenetic, metabolic, and genomic characteristics. In pancreatic ductal adenocarcinoma, USP21 acts as an oncogene by stabilizing the long isoform of Transcription Factor 7, thereby activating the Wnt signaling pathway. This study aims to inhibit activation of this pathway through computer-aided drug discovery. Accordingly, four libraries of compounds were designed to target the USP21's catalytic domain (Cys221, His518, Asp534), responsible for its deubiquitinating activity. Main methodsUtilizing an array of computer-aided drug design methodologies, such as molecular docking, virtual screening, principal component analysis, molecular dynamics simulation, and dynamic cross-correlation matrix, the structural and functional characteristics of the USP21-inhibitor complex were examined. Following the evaluation of the binding affinities, 20 potential ligands were selected, and the best ligand was subjected to additional molecular dynamics simulation study. Key findingsThe results indicated that the ligand-bound USP21 exhibited reduced structural fluctuations compared to the unbound form, as evident from RMSD, RMSF, Rg, and SASA graphs. ADMET analysis of the top ligand showed promising pharmacokinetic and pharmacodynamic profiles, good bioavailability, and low toxicity. The stable conformations of the proposed drug when bound to their target cavities indicate a robust binding affinity of −9.3 kcal/mol. The drug exhibits an elevated pKi value of 6.82, a noteworthy pIC50 value of 5.972, and a pKd value of 6.023 proving its high affinity and inhibitory potential towards the target. SignificanceIn-vitro testing of the top compound (MOLHYB-0436) could lead to its use as a potential treatment for pancreatic cancer.

Heat transport in SiCOH thin films: an experimental and molecular dynamics study

Carbon-doped silicon dioxide (SiCOH) film is currently regarded as one of the most promising low-k materials in the integrated circuits (ICs) industry for advanced technology nodes. However, there have been limited studies on the thermal properties of SiCOH compared to its electrical and mechanical properties. In this study, we investigate the thermal conductivity of SiCOH thin films through molecular dynamics simulations (MD) and experimental characterizations. Our findings indicate that the size effect on thermal conductivity at 300 K is negligible when the thickness of SiCOH film is less than 20 nm. Additionally, we observe a contrasting temperature dependence law for the thermal conductivity of SiCOH thin films compared to crystal SiO2 thin films. Furthermore, we demonstrate a significant decrease in thermal conductivity with increasing porosity in SiCOH films; specifically, an increase in porosity from 5.35% to 42.77% results in a 60% reduction in thermal conductivity. Moreover, we validate our simulation results by characterizing the thermal conductivity of SiCOH using 3 ω method.