Journal of molecular graphics & modelling最新文献_第4页

Comparative study of various molecular feature representations for solvation free energy predictions of neutral species 用于预测中性物种溶解自由能的各种分子特征表示的比较研究。

IF 2.7 4区生物学

Journal of molecular graphics & modelling Pub Date : 2024-11-01 DOI: 10.1016/j.jmgm.2024.108901

Valerii V. Isaev , Yury Minenkov

{"title":"Comparative study of various molecular feature representations for solvation free energy predictions of neutral species","authors":"Valerii V. Isaev , Yury Minenkov","doi":"10.1016/j.jmgm.2024.108901","DOIUrl":"10.1016/j.jmgm.2024.108901","url":null,"abstract":"<div><div>Predicting molecular properties with the help of Neural Networks is a common way to substitute or enhance comprehensive quantum-chemical calculations. One of the problems facing researchers is the choice of vectorization approach to representing the solvent and the solute for the estimator model. In this work, 10 different approaches have been investigated for both organic solute and solvent including vectorizers that relied on macroscopic parameters, functional groups classification, molecular graphs, or atomic coordinates. A variation of the Bag of Bonds approach called JustBonds, trained on the MNSol database, showed the best overall performance resulting in RMSD <2 kcal/mol for the blind dataset that contains the solutes not presented in the training subset and <1 kcal/mol on records from Solv@TUM database, which is close to contemporary continuum models. We have also demonstrated that the most important bags usually contain heteroatom and play a key role in the solvation process. Furthermore, the small role of solvent vectorization was demonstrated and revealed that approaches based on functional groups or macroscopic solvent parameters are often enough to efficiently represent solvent media.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"134 ","pages":"Article 108901"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603822","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}

引用次数: 0

Effect of channel roughness on the particle diffusion and permeability of carbon nanotubes in reverse electrodialysis process applying molecular dynamics simulation 应用分子动力学模拟研究反向电渗析过程中通道粗糙度对碳纳米管颗粒扩散和渗透性的影响。

IF 2.7 4区生物学

Journal of molecular graphics & modelling Pub Date : 2024-10-30 DOI: 10.1016/j.jmgm.2024.108899

Yabing Li , Ali B.M. Ali , Nelly Esther Flores Tapia , Nargiza Kamolova , Soheil Salahshour , Rozbeh Sabetvand

{"title":"Effect of channel roughness on the particle diffusion and permeability of carbon nanotubes in reverse electrodialysis process applying molecular dynamics simulation","authors":"Yabing Li , Ali B.M. Ali , Nelly Esther Flores Tapia , Nargiza Kamolova , Soheil Salahshour , Rozbeh Sabetvand","doi":"10.1016/j.jmgm.2024.108899","DOIUrl":"10.1016/j.jmgm.2024.108899","url":null,"abstract":"<div><div>Innovative technology and methods are crucial for making pure and refreshing water. Two main methods are present to delete soluble salts from water: membrane processes and thermal processes. A beneficial membrane technique is reverse electrodialysis. This research used molecular dynamics (MD) simulation to investigate how channel roughness affected particle diffusion and permeability in carbon nanotubes (CNTs) via the reverse electrodialysis process. The results indicate that adding roughness in the CNT duct increased the force between the primary fluid and the duct. Using an armchair-edged CNT structure maximized the electric current in the sample. Furthermore, the roughness increased the intensity of force in the channel, which was due to gravity, leading to a decrease in the mobility of fluid particles. Additionally, several broken hydrogen bonds inside the simulation box increased from 116 to 128 in the duct sample with roughness.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"134 ","pages":"Article 108899"},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568948","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}

引用次数: 0

Molecular dynamics simulations, essential dynamics and MMPBSA to evaluate natural compounds as potential inhibitors for AccD6, a key drug target in the fatty acid biosynthesis pathway in Mycobacterium tuberculosis 利用分子动力学模拟、基本动力学和 MMPBSA 评估天然化合物作为 AccD6（结核分枝杆菌脂肪酸生物合成途径中的一个关键药物靶点）潜在抑制剂的效果

IF 2.7 4区生物学

Journal of molecular graphics & modelling Pub Date : 2024-10-28 DOI: 10.1016/j.jmgm.2024.108898

Chandra Jyoti Singha, Ramadas Krishna

{"title":"Molecular dynamics simulations, essential dynamics and MMPBSA to evaluate natural compounds as potential inhibitors for AccD6, a key drug target in the fatty acid biosynthesis pathway in Mycobacterium tuberculosis","authors":"Chandra Jyoti Singha, Ramadas Krishna","doi":"10.1016/j.jmgm.2024.108898","DOIUrl":"10.1016/j.jmgm.2024.108898","url":null,"abstract":"<div><div>Antibiotic resistance in <em>Mycobacterium tuberculosis</em>, the primary causative agent of the tuberculosis disease is an ever growing threat especially in developing and underdeveloped countries. Isoniazid is a commonly used first line anti-tuberculosis drug used during the first phase of tuberculosis treatment. However, due to its improper use, many strains of <em>Mycobacterium tuberculosis</em> have acquired resistance to the drug. Advancements in next generation sequencing technologies, such as transcriptomics have paved way for identifying alternative drug targets based on the differential expression pattern of genes. Therefore, this study makes use of RNA-Seq data of <em>Mycobacterium tuberculosis</em> isolates treated with different concentrations of isoniazid to identify genes that can be proposed as drug targets. From the differential expression analysis, it was observed that four genes were significantly upregulated under all the conditions. Among the four genes, <em>accD6</em> was selected as the drug target for virtual screening and molecular dynamics studies, because of its role in fatty acid elongation and contribution to the synthesis of mycolic acids. The protein-protein interaction network and gene ontology based functional enrichment studies show an enrichment in fatty acid biosynthesis related pathways. Furthermore, virtual screening studies successfully screened the top three natural inhibitor molecules with satisfactory ADME properties and a better glide score than the reference compound, NCI-172033. The trajectory analysis, essential dynamics studies and MMPBSA analysis, concluded that among the hit molecules, NPC41982, a thiazole derivative showed the most promising results and can be considered as a potential drug candidate.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"134 ","pages":"Article 108898"},"PeriodicalIF":2.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561017","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}

引用次数: 0

Molecular engineering on tyrian puprle natural dye as TiO2 based fined tuned photovoltaic dye material: DFT molecular analysis 作为基于二氧化钛的微调光伏染料材料的酪朊蛹天然染料的分子工程学：DFT 分子分析

IF 2.7 4区生物学

Journal of molecular graphics & modelling Pub Date : 2024-10-26 DOI: 10.1016/j.jmgm.2024.108894

Cihat Güleryüz , Duha M. Hasan , Masar A. Awad , Azal S. Waheeb , Abrar U. Hassan , Ayesha Mohyuddin , Hussein A.K. Kyhoiesh , Mohammed T. Alotaibi

{"title":"Molecular engineering on tyrian puprle natural dye as TiO2 based fined tuned photovoltaic dye material: DFT molecular analysis","authors":"Cihat Güleryüz , Duha M. Hasan , Masar A. Awad , Azal S. Waheeb , Abrar U. Hassan , Ayesha Mohyuddin , Hussein A.K. Kyhoiesh , Mohammed T. Alotaibi","doi":"10.1016/j.jmgm.2024.108894","DOIUrl":"10.1016/j.jmgm.2024.108894","url":null,"abstract":"<div><div>In this research, molecular modification is employed to see the enhancement in the efficiency of Tyrian Purple (TP), a natural dye, for organic photovoltaic materials. By using Density Functional Theory (DFT) based molecular modeling, seven new structures are designed with pi spacer to extend electron donor moieties. Teheir Frontier Molecular Orbital (FMO) analysis demonstartes their charges with a similar pattern of distributions over their Highest Occupied and Lowed Unocuupied Molecular Orbitals (HOMO/lUMO). This analysls also show their energy gaps (E<sub>gaps</sub>) to range around 2.97–3.02 eV. Their maximum absorption wavelength (<em>λ<sub>max</sub></em>) demosntartes 486–490 nm range to indicate their tendency of absorbing light efficiently. Their Transition Density Matrix (TDM) analysis also reveals their facile electronic transitions without a significant charges over spacers. From calculating their photovoltaic paramters, their Light Harvesting Efficiency (LHE) reaches to 72.4–95.5 %. Also their Open Circuit Voltage (V<sub>oc</sub>) varies across 1.16–1.34 V. It is found that dyes actively adsorb onto TiO<sub>2</sub> clusters to demonstrate their promise for tuning their Conduction Band (CB). This research is an effort for to evaluate the structural correlations to the develop photovoltaic materials through molecular-level design and optimization.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"134 ","pages":"Article 108894"},"PeriodicalIF":2.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561018","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}

引用次数: 0

Unraveling the adsorption dynamics of asphaltene molecules on silica surfaces 揭示沥青分子在二氧化硅表面的吸附动力学。

IF 2.7 4区生物学

Journal of molecular graphics & modelling Pub Date : 2024-10-26 DOI: 10.1016/j.jmgm.2024.108897

Fengfeng Gao

{"title":"Unraveling the adsorption dynamics of asphaltene molecules on silica surfaces","authors":"Fengfeng Gao","doi":"10.1016/j.jmgm.2024.108897","DOIUrl":"10.1016/j.jmgm.2024.108897","url":null,"abstract":"<div><div>Understanding the adsorption behavior of heavy oil components on reservoir solids is crucial for improving oil recovery, yet the molecular mechanism remains unclear. This study used molecular dynamics simulations to explore the adsorption kinetics and thermodynamics of asphaltene molecules on silica surfaces. The adsorption process was divided into three stages: free, adsorption, and equilibrium. In the adsorption stage, asphaltenes must pass through two dense hydration layers and adhere to the silica surface in a flat configuration. Carboxyl groups increase asphaltene hydrophilicity, raising interaction energy with water molecules and hindering adsorption. In addition, two distinct hydration layers of water molecules on the silica surface. The first hydration layer, with a peak density of 2000 kg m<sup>−3</sup>, was located around 0.6 nm from the surface, driven by hydrogen bonding between Si-OH groups and water molecules. The second layer, found at 1.44–1.80 nm, had a lower density of 1200 kg m<sup>−3</sup>, formed through hydrogen bonding between water molecules. This study aims to enhance the understanding of the physicochemical mechanisms governing oil droplet adsorption on silica surfaces, potentially informing the design of improved oil recovery strategies.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"134 ","pages":"Article 108897"},"PeriodicalIF":2.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522153","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}

引用次数: 0

QSPR modeling to predict surface tension of psychoanaleptic drugs using the hybrid DA-SVR algorithm 利用 DA-SVR 混合算法建立 QSPR 模型，预测精神药物的表面张力。

IF 2.7 4区生物学

Journal of molecular graphics & modelling Pub Date : 2024-10-23 DOI: 10.1016/j.jmgm.2024.108896

Meriem Ouaissa , Maamar Laidi , Othmane Benkortbi , Hasmerya Maarof

{"title":"QSPR modeling to predict surface tension of psychoanaleptic drugs using the hybrid DA-SVR algorithm","authors":"Meriem Ouaissa , Maamar Laidi , Othmane Benkortbi , Hasmerya Maarof","doi":"10.1016/j.jmgm.2024.108896","DOIUrl":"10.1016/j.jmgm.2024.108896","url":null,"abstract":"<div><div>A robust Quantitative Structure-Property Relationship (QSPR) model was presented to predict the surface tension property of psychoanaleptic (psychostimulant and antidepressant) drugs. A dataset of 112 molecules was utilized, and three feature selection methods were applied: genetic algorithm combined with Ordinary Least Squares (GA-OLS), Partial Least Squares (GA-PLS), and Support Vector Machines (GA-SVM), each identifying ten pertinent AlvaDesc descriptors. The models were constructed using the Dragonfly Algorithm combined with the Support Vector Regressor (DA-SVR), with the GA-SVM-based model emerging as the top performer. Rigorous statistical metrics validate its superior predictive accuracy (<em>R</em><sup><em>2</em></sup> = 0.98142, <em>Q</em><sup><em>2</em></sup><sub><em>LOO</em></sub> = 0.98142, <em>RMSE</em> = 1.12836, <em>AARD</em> = 0.78746). Furthermore, an external test set of ten compounds was employed for model validation and extrapolation, along with assessing the applicability domain, further underscoring the model’s reliability. The selected descriptors (X0Av, VE1sign_B(e), ATSC1e, MATS6v, P_VSA_ppp_A, TDB01u, E1s, R2m+, N-067, SssO) collectively elucidate the key structural factors influencing surface tension in the studied drugs. The model provides excellent predictions and can be used to determine the surface tension of new psychoanaleptic drugs. Its outcomes will guide the design of novel medications with targeted surface tension properties.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"134 ","pages":"Article 108896"},"PeriodicalIF":2.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545963","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}

引用次数: 0

Evaluating interaction energy versus electron density relationships to estimate inter and intramolecular H-bonding 评估相互作用能与电子密度的关系，以估算分子间和分子内的氢键。

IF 2.7 4区生物学

Journal of molecular graphics & modelling Pub Date : 2024-10-22 DOI: 10.1016/j.jmgm.2024.108895

Murillo H. Queiroz , Suelen A. Santos , Joel L. Nascimento , Bruno S. Sampaio , Tiago V. Alves , Roberto Rivelino

{"title":"Evaluating interaction energy versus electron density relationships to estimate inter and intramolecular H-bonding","authors":"Murillo H. Queiroz , Suelen A. Santos , Joel L. Nascimento , Bruno S. Sampaio , Tiago V. Alves , Roberto Rivelino","doi":"10.1016/j.jmgm.2024.108895","DOIUrl":"10.1016/j.jmgm.2024.108895","url":null,"abstract":"<div><div>We investigate the computational effects on the relationships between interaction energy (ΔE) and electron density (ρ), at the critical point obtained from 19 intermolecular H-bonded dimers, to estimate inter and intramolecular interactions of larger H-bonded systems. Our analysis examines basis set superposition error (BSSE) effects, dispersion energy corrections, and the exchange-correlation energy model on the ΔE vs. ρ linear regressions. The calculations were carried out within density functional theory (DFT) combined with the 6-31+G(d,p) and def2-TZVPP basis sets. This procedure quantifies the average effects of BSSE for different levels of approximation, and underscore the sensitivity of the ΔE estimation together with dispersion corrections. This is valuable for the development of DFT-based estimators of multiple interaction energies of large H-bonded systems with low computational cost. We have applied this procedure by analyzing H-bonded biological molecules, such as DNA base pairs, an asparagine side chain, and an AZT molecule. Our estimated H-bond interaction energies are in agreement with previous studies, and emphasize the importance of methodological considerations for accurately predicting interaction energies using DFT combined with topological parameters.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"134 ","pages":"Article 108895"},"PeriodicalIF":2.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502240","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}

引用次数: 0

Molecular dynamics simulations of hydrogen-bonded network structures of polybenzoxazines in the gas phase and aqueous solution 气相和水溶液中聚苯并恶嗪氢键网络结构的分子动力学模拟。

IF 2.7 4区生物学

Journal of molecular graphics & modelling Pub Date : 2024-10-18 DOI: 10.1016/j.jmgm.2024.108893

Pakuna Panbo , Uthen Thubsuang , Apirak Payaka

{"title":"Molecular dynamics simulations of hydrogen-bonded network structures of polybenzoxazines in the gas phase and aqueous solution","authors":"Pakuna Panbo , Uthen Thubsuang , Apirak Payaka","doi":"10.1016/j.jmgm.2024.108893","DOIUrl":"10.1016/j.jmgm.2024.108893","url":null,"abstract":"<div><div>The crucial role of the amine functional group at the Mannich bridge of polybenzoxazines (PBZs) has been reported to be responsible for their hydrogen-bonded network structures. However, they have not been thoroughly studied in an aqueous solution and at the atomistic level. In this study, molecular dynamics simulations were applied to investigate the formation of hydrogen bond interactions of PBZs prepared from bisphenol A/methylamine (m-PBZ), bisphenol A/aniline-based (a-PBZ), and bisphenol A/2-(methylamino)ethylamine (e-PBZ). Based on the simulation results, the hydrogen-bonded network structures of the PBZs interfered with water molecules, leading to less compaction of the PBZ structure in the aqueous solution. The hydrogen bonding species of the m-PBZ and a-PBZ structures consisted of the –OH<sup>…</sup>N (Mannich) and –OH<sup>…</sup>O intramolecular interactions. However, for e-PBZ, the –OH<sup>…</sup>O species was not present, but the 2-(ethylamino)ethylamine substituent formed more hydrogen bonding species than those of m-PBZ and a-PBZ. Additionally, the intermolecular hydrogen bond interactions of the PBZs and water molecules were not detected in any of the aqueous solution simulations.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"134 ","pages":"Article 108893"},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502241","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}

引用次数: 0

Designing of new functionalized imidazolium based ionic liquids attached to the antracene derivatives and investigation on the influence of intramolecular hydrogen bondings in anions on their intermolecular hydrogen bondings and some of the other properties: A DFT M06-2X-GD3 study 设计附着于蒽衍生物的新型官能化咪唑离子液体，并研究阴离子中分子内氢键对其分子间氢键及其他一些性质的影响：DFT M06-2X-GD3 研究。

IF 2.7 4区生物学

Journal of molecular graphics & modelling Pub Date : 2024-10-18 DOI: 10.1016/j.jmgm.2024.108885

Farzad Alijani Chakoli, Khatereh Ghauri, Farhad Shirini

{"title":"Designing of new functionalized imidazolium based ionic liquids attached to the antracene derivatives and investigation on the influence of intramolecular hydrogen bondings in anions on their intermolecular hydrogen bondings and some of the other properties: A DFT M06-2X-GD3 study","authors":"Farzad Alijani Chakoli, Khatereh Ghauri, Farhad Shirini","doi":"10.1016/j.jmgm.2024.108885","DOIUrl":"10.1016/j.jmgm.2024.108885","url":null,"abstract":"<div><div>To promote the development of new functionalized ionic liquids, it is necessary to get a deeper insight into their features of physicochemical and electronic and molecular structure. In this study, the interaction energies and structural and vibrational frequencies parameters in accompanied with some of the physiochemical, electronic and optic attributes of ionic liquids designed by the covalently attachement of imidazolium to anthracene derivatives ([X-AnMIM][A2] and [X-AnMIM][A3], X: NH<sub>2</sub>, OH, OMe, H, Cl, CHO, CN and NO<sub>2</sub>) ILs have been evaluated. Two conjugate bases of acids 1,3,5-pentanetriol (A2) and 3-(2-hydroxyethyl)-1,3,5-pentanetriol (A3) are used as anions which have two and three intramolecular hydrogen bonds, respectively. Based on the results of calculations at M06-2X-GD3/6–311++(d,p) level of theory, the differences in these properties in addition to the structural type of anions and cations can be attributed to the cation-anion, intra and intermolecular hydrogen bonding, interactions in ionic liquids. The results depict that the ILs based on A2 anions form stronger hydrogen bonds with [X-AnMIM]<sup>+</sup> cations. The potency of interaction between cations and anion reduces with the increasement in the number of intramolecular hydrogen bonds and also decreasement in the basic strength in the anionic part. A clear red shift is observed between [X-AnMIM][A2] and [X-AnMIM][A3] ILs and isolated anthracene, which is a clear manifestation of the effect of the imidazolium cation on the electronic energy levels of anthracene. It can be expected that the studied ILs are not electrochemically stable during the electrochemistry applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"134 ","pages":"Article 108885"},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545962","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}

引用次数: 0

Engineering affinity of humanized ScFv targeting CD147 antibody: A combined approach of mCSM-AB2 and molecular dynamics simulations 人源化 ScFv 靶向 CD147 抗体的亲和力工程：mCSM-AB2 与分子动力学模拟相结合的方法

IF 2.7 4区生物学

Journal of molecular graphics & modelling Pub Date : 2024-10-13 DOI: 10.1016/j.jmgm.2024.108884

Thanathat Pamonsupornwichit , Kanchanok Kodchakorn , Piyachat Udomwong , Kanokporn Sornsuwan , Anuwat Weechan , On-anong Juntit , Piyarat Nimmanpipug , Chatchai Tayapiwatana

{"title":"Engineering affinity of humanized ScFv targeting CD147 antibody: A combined approach of mCSM-AB2 and molecular dynamics simulations","authors":"Thanathat Pamonsupornwichit , Kanchanok Kodchakorn , Piyachat Udomwong , Kanokporn Sornsuwan , Anuwat Weechan , On-anong Juntit , Piyarat Nimmanpipug , Chatchai Tayapiwatana","doi":"10.1016/j.jmgm.2024.108884","DOIUrl":"10.1016/j.jmgm.2024.108884","url":null,"abstract":"<div><div>This study aims to assess the effectiveness of mCSM-AB2, a graph-based signature machine learning method, for affinity engineering of the humanized single-chain Fv anti-CD147 (HuScFvM6-1B9). In parallel, molecular dynamics (MD) simulations were used to gain valuable insights into the dynamics and affinity of the HuScFvM6-1B9-CD147 complex. The result analysis involved integrating free energy changes calculated from the mCSM-AB2 with binding free energy predictions from MD simulations. The simulated structures of the modified HuScFvM6-1B9-CD147 domain 1 complex from MD simulations were used to highlight critical residues participating in the binding surface. Interestingly, alterations in the pattern of amino acids of HuScFvM6-1B9 at the complementarity determining regions interacting with the 31EDLGS35 epitope were observed, particularly in mutants that lost binding activity. The predicted mutants of HuScFvM6-1B9 were subsequently engineered and expressed in <em>E. coli</em> for subsequent binding property validation. Compared to WT HuScFvM6-1B9, the mutant HuScFvM6-1B9<sup>L1:N32Y</sup> exhibited a 1.66-fold increase in binding affinity, with a K<sub>D</sub> of 1.75 × 10<sup>−8</sup> M. While mCSM-AB2 demonstrates insignificant improvement in predicting binding affinity enhancements, it excels at predicting negative effects, aligning well with experimental validation. In addition to binding free energies, total entropy was considered to explain the discrepancy between mCSM-AB2 predictions and experimental results. This study provides guidelines and identifies the limitations of mCSM-AB2 and MD simulations in antibody engineering.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"133 ","pages":"Article 108884"},"PeriodicalIF":2.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432346","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}

引用次数: 0