Journal of molecular graphics & modelling最新文献

{"title":"Absorption study of fat-soluble vitamins into dipalmitoylphosphatidylcholine (DPPC) bilayer by MD simulations.","authors":"Chanya Phromchaloem, Narissara Na Nakorn, Laksamee Muensritharam, Warabhorn Boonyarat","doi":"10.1016/j.jmgm.2024.108929","DOIUrl":"https://doi.org/10.1016/j.jmgm.2024.108929","url":null,"abstract":"<p><p>Retinol, α-tocopherol and phylloquinone (vitamins A, E, and K) are presented in high concentrations within the chloroplast and leaves of most plants. They are fat-soluble vitamins and absorb similarly to other dietary lipids. Because the molecular mechanism of retinol, α-tocopherol, and phylloquinone absorption is still unknown, this work aims to investigate the distribution of these vitamins at the water/membrane interface using molecular dynamics (MD) simulations. Structures and variations of the hydroxyl group in vitamins are the keys to the investigation of the absorption process. Binding orientations, favorable binding sites, interactions, and diffusion of vitamins were identified. All vitamins spontaneously penetrate the lipid bilayer. According to simulations, the formation of the hydrogen bonding interaction with the phosphate group of DPPC during absorption requires a hydroxyl group of retinol and tocopherol. Therefore, retinol has -OH group at the tail of the structure and shows the highest structural flexibility of retinol, broadest tilt angle toward the lipid membrane, and highest diffusion coefficient. Finally, retinol plugs its head group into the hydrocarbon core of the lipid bilayer. In the case of α-tocopherol, the hydroxyl at the head group produces α-tocopherol, which moves through one leaflet of the lipid membrane and is stabilized in the opposite leaflet. Interestingly, phylloquinone, a molecule without a hydroxyl group, stabilizes close to a phosphate group without hydrogen bond formation. The head group of phylloquinone penetrates at a precise tilting angle of 120°. High retention of phylloquinone inside gel-phase DPPC is suggested by its low diffusion coefficient. MD simulations reveal the characteristics of three fat-soluble vitamins during absorption through the phospholipid membrane. This information is useful as a guideline to improve the absorption of drugs along the membrane.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"135 ","pages":"108929"},"PeriodicalIF":2.7,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adsorption of sulfur mustard on the transition metals (TM = Ti²⁺, Cr²⁺, Fe^2+, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺) porphyrins induced in carbon nanocone (TM-PCNC): Insight from DFT calculation.","authors":"Ahmad Saeed Hessen, Nahed Mahmood Ahmed Alsultany, Hala Bahir, A Husein Adthab, Somayeh Soleimani-Amiri, Sheida Ahmadi, Esmail Vessally, Azadeh Khanmohammadi","doi":"10.1016/j.jmgm.2024.108928","DOIUrl":"https://doi.org/10.1016/j.jmgm.2024.108928","url":null,"abstract":"<p><p>The density functional theory (DFT) method is applied to investigate the ability of transition metals porphyrins induced in carbon nanocone (TM-PCNC, TM = Ti²⁺, Cr²⁺, Fe²⁺, Co²⁺, Ni²⁺, Cu²⁺, and Zn²⁺) for identifying and eliminating undesirable SM molecules from the surrounding. The sulfur mustard is effectively adsorbed onto the surface of nanocones through a chemical process. Based on the DFT calculations, the Ti-PCNC displays an appropriate percentage change in energy gap (%ΔE_g = 11.82 and 14.67), thus making it a promising candidate for possessing sensing capabilities towards the sulfur mustard. According to the acquired findings, it can be deduced that the work function of nanocones exhibits minimal alterations after the adsorption of sulfur mustard. This signifies that nanocones may not serve as a suitable work function sensor for sulfur mustard detection. In addition, when the UV-visible spectra of pristine Ti-PCNC are compared with its complexes, it is found that sulfur mustard adsorption does not change the nanocones spectra but increases the number of absorption lines.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"135 ","pages":"108928"},"PeriodicalIF":2.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling Interleukin-1β inhibition: Computational insights into anti-inflammatory compound selection for inflammatory disorders.","authors":"Madiha Sardar, Ali Raza Siddiqui, Nadeem Ahmad, Mamona Mushtaq, Sehrish Shafeeq, Mohammad Nur-E-Alam, M Nabeel Ghayur, Zaheer Ul-Haq","doi":"10.1016/j.jmgm.2024.108925","DOIUrl":"https://doi.org/10.1016/j.jmgm.2024.108925","url":null,"abstract":"<p><p>The multifaceted impact of IL-1β has been proposed to have a central role in a spectrum of immunological responses spanning physiological reactions to aggressive inflammatory reactions and autoimmune disorders. Once IL-1β binds to its cognate receptor it initiates IL-1R1/TLR4 signaling cascade, leading to transcriptional modifications that sustain the inflammatory response. Extensive structural and functional investigations on IL-1β have yielded various inhibitors aimed at disrupting the formation of ligand receptor complex. Unfortunately, most have proven unsuccessful in clinical trials. Therefore, directing efforts towards IL-1β/IL-1R1 presents a unique opportunity to formulate an alternative therapy for the treatment of inflammatory disorders. In view of this, the present study aimed to identify small molecules obstructing protein-protein interactions (PPIs) to impede heterocomplex formation. In this context, a search query was formulated by integrating a ligand-based pharmacophore mapping alongside a multi-stage molecular docking to assess the potential of the predicted hits in terms of binding modes within the targeted cavity of the IL-1β and the associated binding affinities. Thus, via a stepwise screening process starting from an initial pool of 40,000 compounds, 8 potential hits were identified for detailed atomic studies employing molecular dynamic simulation encompassing a total time frame of 0.9 μs. The investigation in dynamic behavior was followed by the estimation of free energies using molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations. The stability matrices revealed that the chosen virtual hits possess a notable potential to hinder the complex formation between IL-1β/IL-1RI. The average backbone deviations recorded for the conformational ensembles of the ligand free IL-1β/IL-1RI exhibited significant dynamics, featuring the average value of 0.35 nm. Conversely, the identified hits particularly, inhouse-2603 and inhouse-1325 demonstrated a high degree of stability with mean values of 0.32 ± 0.05, 0.31 ± 0.03, respectively. The residue-wise fluctuations were maximum for Compound-1303, with the mean value of 0.31 nm and minimal for Compound-2691 with the mean value 0.21 nm. The MMPBSA revealed the highest binding energy of -89.50 ± 10.63, and -81.32 ± 14.9 kcal/mol, for the IL-1β/IL-1RI complex with compound-2603, and Compound-1325 respectively. The principal component analysis (PCA) in conjunction with free energy landscape (FEL) further shed light on the conformational space in terms of energetic stability. Considering the essential role of IL-1β in mediating several inflammatory cascades, it is proposed that the identified PPI inhibitors since demonstrated stable behavior and promising attributes in regard to inhibitory potential as outlined by mechanistic exploration, may serve as new chemotypes for the future exploration aimed at mitigation inflammatory disorders.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"135 ","pages":"108925"},"PeriodicalIF":2.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular networks via reduced reverse degree approach.","authors":"Muhammad Mudassar Hassan, Xiang-Feng Pan, De-Min Yu, Muhammad Shoaib Sardar","doi":"10.1016/j.jmgm.2024.108917","DOIUrl":"https://doi.org/10.1016/j.jmgm.2024.108917","url":null,"abstract":"<p><p>Porphyrazine and tetrakis porphyrazine are examples of organic compounds with complicated structures of rings. Physicists and chemical researchers have been interested in these structures because of their highly conjugated systems, which lead to peculiar optical and electrical characteristics. These structures are the fundamental components of molecular electronics, sensors, functional materials, and catalysis, among other scientific fields. The idea behind modeling molecules as networks is to calculate the topological index, where atoms are nodes and bonds are links. We can use multiple techniques and algorithms to calculate the topological index. We have used the reduced reverse degree-based approach for estimating the topological indices of the Porphyrazine and Tetrakis porphyrazine structures. The purpose of calculating the reduced reverse degree-based topological indices is to quantify the molecular topology of the mentioned structures. In future research, we can also use these indices in SAR/QSAR modeling of porphyrazine and tetrakis porphyrazine. These indices can also provide comparative analysis and descriptors for predicting chemical behavior, which is useful in material science applications and drug designs. In this study, we present a formula for calculating reduced reverse degree-based topological indices for porphyrazine and tetrakis porphyrazine, including the reduced reverse geometric arithmetic index, reduced reverse general Randić index, reduced reverse Balaban index, reduced reverse redefined Zagreb index, reduced reverse forgotten index, reduced reverse hyper-Zagreb index, and reduced reverse atom-bond connectivity index. Before the conclusion, there is a graph-theoretical analysis and comparison to ascertain the essential significance and validate the obtained results. This research helps to create novel materials for a variety of applications and sheds light on the structural and chemical characteristics of these molecular networks.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"135 ","pages":"108917"},"PeriodicalIF":2.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brussonol and komaroviquinone as inhibitors of the SARS-CoV-2 Omicron BA.2 variant spike protein: A molecular docking, molecular dynamics, and quantum biochemistry approach.","authors":"Samuel J M Santos, Antoninho Valentini","doi":"10.1016/j.jmgm.2024.108914","DOIUrl":"https://doi.org/10.1016/j.jmgm.2024.108914","url":null,"abstract":"<p><p>Since late 2019, humanity has faced the challenges posed by the COVID-19 pandemic, caused by the SARS-CoV-2 virus. The continuous evolution of SARS-CoV-2 has led to the emergence of multiple Variants of Concern (VOCs) and Variants of Interest (VOIs), posing significant risks to global health. SARS-CoV-2 infects host cells via the angiotensin-converting enzyme 2 (ACE2) receptors, facilitated by the spike (S) protein. Icetexane diterpenes, including brussonol and komaroviquinone, exhibit notable anti-inflammatory, antibacterial, antiviral, antiproliferative, and anticancer properties. Recent research has explored their potential as inhibitors of the SARS-CoV-2 3Clpro protease, showing promising efficacy comparable to Nirmatrelvir. This study investigates brussonol and komaroviquinone as potential inhibitors of the SARS-CoV-2 Omicron BA.2 variant spike protein using molecular docking, molecular dynamics simulations, and quantum biochemistry approaches. The stability and interaction energies of brussonol, komaroviquinone, and mefloquine with the SARS-CoV-2 Omicron BA.2 variant spike protein were evaluated. RMSD analysis demonstrated that komaroviquinone and mefloquine maintain more stable binding poses with the spike protein compared to various NAGs and glycans. Electrostatic potential maps revealed significant interactions with ASN603, a critical residue for ligand binding efficacy. Furthermore, this study addresses a gap in current research, as no studies were found that simulate the trimer of the SARS-CoV-2 BA.2 variant spike protein. Most existing studies focus on the monomer and often exclude the NAGs and glycans. This research underscores the importance of maintaining the NAGs and glycans in the trimer simulations, providing a more accurate representation of the protein's structure and its interactions with ligands. The findings indicate that both komaroviquinone and brussonol exhibit higher binding affinities compared to mefloquine. This study provides valuable insights into the molecular interactions of these compounds, highlighting their potential for further development as antiviral agents against SARS-CoV-2.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"135 ","pages":"108914"},"PeriodicalIF":2.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation on the effect of Co doping on structure, electronic, and hydrogen storage properties of Mg2FeH6","authors":"Li Ping Ding ,&nbsp;Fei Yue Qiao ,&nbsp;Hong Yuan Xu ,&nbsp;Shao Fei Lei ,&nbsp;Peng Shao","doi":"10.1016/j.jmgm.2024.108916","DOIUrl":"10.1016/j.jmgm.2024.108916","url":null,"abstract":"<div><div>Metal hydrides, particularly magnesium-based materials, exhibit excellent hydrogen storage capabilities. Among these, Mg₂FeH₆ stands out for its high hydrogen storage capacity, but it faces limitations due to low thermodynamic stability and high hydrogen desorption temperature. To overcome these challenges, we investigated the potential of Co doping to improve hydrogen storage properties. Based on first-principles calculations, we systematically explored the structures, electronic properties and hydrogen storage capabilities of a novel Mg-Fe-Co-H alloy. We found that Co doping significantly reduced the band gap by 1.14 eV, promoting electron transitions and accelerating hydrogen desorption kinetics. Additionally, Co doping alters the Fe-H interaction, increasing bond lengths and facilitating the hydrogen dissociation. Although Co doping slightly decreases hydrogen storage capability of Mg₂FeH₆ (from 5.45 <em>wt</em>% to 5.32 <em>w</em>t%), it significantly lowers desorption temperature from 651 K (Mg₂FeH₆) to 543 K (Mg₂Fe_1/8Co_7/8H₆). This study highlights the innovative potential of Co doping to enhance the performance of Mg₂FeH₆-based hydrogen storage materials, offering promising prospects for advancing hydrogen energy technologies.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"135 ","pages":"Article 108916"},"PeriodicalIF":2.7,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel in silico approach for identifying multi-target JAK/STAT inhibitors as anticancer agents","authors":"Alessia Bono ,&nbsp;Gabriele La Monica ,&nbsp;Federica Alamia ,&nbsp;Antonino Lauria ,&nbsp;Annamaria Martorana","doi":"10.1016/j.jmgm.2024.108913","DOIUrl":"10.1016/j.jmgm.2024.108913","url":null,"abstract":"<div><div>Apoptosis, or programmed cell death, plays a pivotal role in maintaining cellular homeostasis by eliminating damaged or surplus cells. Dysregulation of signaling pathways, such as JAK/STAT, is implicated in various diseases, rendering them attractive therapeutic targets for potential new anticancer drugs. Concurrently, it is imperative to preserve essential proteins like TNF-α and p53 to maintain normal cellular life/death balance. In light of these considerations, this study employs an innovative <em>in silico</em> hybrid and hierarchical virtual screening approach aimed at identifying JAK/STAT multi-target inhibitors as potential anticancer agents for several tumoral diseases. Initially, the Biotarget Predictor Tool is utilized in a combined ON/OFF-target/Multitarget mode using the extensive National Cancer Institute (NCI) database, previously filtered by ADME evaluation tools. Subsequently, Molecular Docking studies are conducted on JAK2, JAK3, and STAT3, facilitating the identification of the most promising compound, <strong>755435</strong>. Finally, Molecular Dynamics Simulations validate the high stability of the potential multitarget inhibitor <strong>755435</strong> in complex with JAK2, JAK3, and STAT3.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"135 ","pages":"Article 108913"},"PeriodicalIF":2.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Keto-enol Tautomerism of hydroxy-substituted arenes: Theoretical study and experimental consequences","authors":"Andrea Kováčová ,&nbsp;Martin Michalík ,&nbsp;Horst Hartmann ,&nbsp;Vladimír Lukeš","doi":"10.1016/j.jmgm.2024.108911","DOIUrl":"10.1016/j.jmgm.2024.108911","url":null,"abstract":"<div><div>In this work, the chemical equilibrium between enol and keto tautomers occurring in phenol, naphthols and selected 29 hydroxy substituted polycyclic aromatic hydrocarbons classified into 4 structural types was investigated. The reaction Gibbs energies were computed using the density functional theory combined with the solvent continuum model. We have demonstrated how the consecutive condensation of benzene rings together with two-dimensional molecular arrangement and the position of the hydroxyl group modifies this equilibrium. The obtained results revealed that the prototropic rearrangement in the electronic ground state is not thermodynamically less probable between two neighbouring condensed benzene rings. The keto form is favoured in linear polycyclic aromatic hydrocarbons for substituted central moieties. The angular molecular structure has the opposite effect. Based on the theoretical energies calculated for room temperature, the tautomerisation p<em>K</em>_T constants and acidity p<em>K</em>_a constants for enols as well as corresponding keto-tautomers were predicted and compared with available experimental values for the water environment. Finally, the possible experimental consequences in respect to the chemical reactivity of studied tautomers were discussed.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"135 ","pages":"Article 108911"},"PeriodicalIF":2.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic variants in the fibronectin type III domain of leptin receptor: Molecular dynamics simulation and structural analysis","authors":"Takashi Kato ,&nbsp;Fumiko Matsuzawa ,&nbsp;Nobuhiro Shojima ,&nbsp;Toshimasa Yamauchi","doi":"10.1016/j.jmgm.2024.108912","DOIUrl":"10.1016/j.jmgm.2024.108912","url":null,"abstract":"<div><div>Several case reports have identified leptin receptor (LEPR) variants associated with severe obesity in humans. However, the structure of LEPR has only been partially understood until recently, and few studies have investigated the detrimental effects of these variants on the protein's three-dimensional structure. Notably, fibronectin type III (FnIII) domains play a crucial role in signal transduction. In this study, we examined the impact of 10 variants within the FnIII domains on LEPR structure using molecular dynamics (MD) simulations and structural analysis. Our 300 ns MD simulations revealed that the C604S variant, which disrupts a key disulfide bond, significantly increased the overall root-mean-square deviation (RMSD) of the FnIII-2 and FnIII-3 domains, indicating destabilization of the interdomain rigidity required for proper signaling. Variants such as P639L, N718S, and W646C also induced abnormal bending and rotational misalignment between the FnIII domains, contributing to interdomain destabilization. Structural analysis identified folding nuclei and demonstrated that L662S, W664R, H684P, and S723F destabilize the internal domain. Variants affecting interdomain resulted in lower-than-expected damage prediction scores by bioinformatics tools. This study is expected to contribute to the elucidation of the disease-causing mechanisms of missense variants in the leptin receptor.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"135 ","pages":"Article 108912"},"PeriodicalIF":2.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dispersion-corrected DFT calculations and dynamic molecular simulations to investigate conformational stability of Lidocaine towards β-CD and HP-β-CD","authors":"Amira Kadri ,&nbsp;Ouassila Attoui Yahia ,&nbsp;Belgacem Bezzina ,&nbsp;Djamel Eddine Khatmi ,&nbsp;Amel Bouzitouna","doi":"10.1016/j.jmgm.2024.108910","DOIUrl":"10.1016/j.jmgm.2024.108910","url":null,"abstract":"<div><div>Lidocaine (LDC) is one of the most important local anaesthesia compounds (LAs), designated to treat acute and chronic pain, especially in clinical applications. In the purpose to improve its lower solubility and bioavailability, numerous researches have been conducted to study the exact mode of association between the LDC molecule and cyclodextrins as drug carriers. Although, the reported structural details on LDC/β-CD and LDC/HP-β-CD inclusion complexes remain largely unexplored. The LDC molecule presents different spatial arrangements inside the hydrophobic cavities of the above-mentioned hosts; either the phenyl moiety or the diethylamino part is totally inserted. Hence, in the present work, we attempt to deepen our understanding about conformational preferences on the binding modes of LDC by investigating the quantum mechanical approach results.</div><div>The PM3 method combined with the pure corrected functional B97D3 revealed the tendency of LDC to enter its diethylamino inside the host, leaving the rest of molecule externally, and consequently form an inclusion complex with HP-β-CD more stable than with the native β-CD by approximately 12 kcal mol⁻¹.</div><div>The probability of partial insertion of LDC is further ascertained by MD simulations investigation running for 500 ns. The trajectory analysis of MD process showed that the diethyl amino fragment is accommodated inside the HP-β-CD's cavity for a significant period (82 % of the simulation time), while it is estimated to be 78 % in the case of LDC/β-CD complex.</div><div>Moreover, the wave function analysis, based on QTAIM, Reduced Density Gradient (RDG) and 2D Fingerprint, illustrated NCIs interactions and sustained the contribution of numerous van der Waals forces and weaker H-bonds interactions in the stability of studied ICs.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"134 ","pages":"Article 108910"},"PeriodicalIF":2.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}