Journal of Computational Chemistry最新文献_第2页

CGPDTA: An Explainable Transfer Learning-Based Predictor With Molecule Substructure Graph for Drug-Target Binding Affinity

IF 3.4 3区化学

Journal of Computational Chemistry Pub Date : 2024-12-09 DOI: 10.1002/jcc.27538

Qing Fan, Yingxu Liu, Simeng Zhang, Xiangzhen Ning, Chengcheng Xu, Weijie Han, Yanmin Zhang, Yadong Chen, Jun Shen, Haichun Liu

{"title":"CGPDTA: An Explainable Transfer Learning-Based Predictor With Molecule Substructure Graph for Drug-Target Binding Affinity","authors":"Qing Fan, Yingxu Liu, Simeng Zhang, Xiangzhen Ning, Chengcheng Xu, Weijie Han, Yanmin Zhang, Yadong Chen, Jun Shen, Haichun Liu","doi":"10.1002/jcc.27538","DOIUrl":"10.1002/jcc.27538","url":null,"abstract":"<div>\u0000 \u0000 Identifying interactions between drugs and targets is crucial for drug discovery and development. Nevertheless, the determination of drug-target binding affinities (DTAs) through traditional experimental methods is a time-consuming process. Conventional approaches to predicting drug-target interactions (DTIs) frequently prove inadequate due to an insufficient representation of drugs and targets, resulting in ineffective feature capture and questionable interpretability of results. To address these challenges, we introduce CGPDTA, a novel deep learning framework empowered by transfer learning, designed explicitly for the accurate prediction of DTAs. CGPDTA leverages the complementarity of drug–drug and protein–protein interaction knowledge through advanced drug and protein language models. It further enhances predictive capability and interpretability by incorporating molecular substructure graphs and protein pocket sequences to represent local features of drugs and targets effectively. Our findings demonstrate that CGPDTA not only outperforms existing methods in accuracy but also provides meaningful insights into the predictive process, marking a significant advancement in the field of drug discovery.\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computer Folding of Parallel DNA G-Quadruplex: Hitchhiker's Guide to the Conformational Space

IF 3.4 3区化学

Journal of Computational Chemistry Pub Date : 2024-12-09 DOI: 10.1002/jcc.27535

Michal Janeček, Petra Kührová, Vojtěch Mlýnský, Petr Stadlbauer, Michal Otyepka, Giovanni Bussi, Jiří Šponer, Pavel Banáš

{"title":"Computer Folding of Parallel DNA G-Quadruplex: Hitchhiker's Guide to the Conformational Space","authors":"Michal Janeček, Petra Kührová, Vojtěch Mlýnský, Petr Stadlbauer, Michal Otyepka, Giovanni Bussi, Jiří Šponer, Pavel Banáš","doi":"10.1002/jcc.27535","DOIUrl":"10.1002/jcc.27535","url":null,"abstract":"Guanine quadruplexes (GQs) play crucial roles in various biological processes, and understanding their folding pathways provides insight into their stability, dynamics, and functions. This knowledge aids in designing therapeutic strategies, as GQs are potential targets for anticancer drugs and other therapeutics. Although experimental and theoretical techniques have provided valuable insights into different stages of the GQ folding, the structural complexity of GQs poses significant challenges, and our understanding remains incomplete. This study introduces a novel computational protocol for folding an entire GQ from single-strand conformation to its native state. By combining two complementary enhanced sampling techniques, we were able to model folding pathways, encompassing a diverse range of intermediates. Although our investigation of the GQ free energy surface (FES) is focused solely on the folding of the all-anti parallel GQ topology, this protocol has the potential to be adapted for the folding of systems with more complex folding landscapes.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.27535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Theoretical investigation of structure and electronic properties in Cisplatin-citrate complexes

IF 3.4 3区化学

Journal of Computational Chemistry Pub Date : 2024-12-07 DOI: 10.1002/jcc.27511

Lipika Oopkaew, Yuwanda Injongkol, Nawee Kungwan, Thanyada Rungrotmongkol

{"title":"Theoretical investigation of structure and electronic properties in Cisplatin-citrate complexes","authors":"Lipika Oopkaew, Yuwanda Injongkol, Nawee Kungwan, Thanyada Rungrotmongkol","doi":"10.1002/jcc.27511","DOIUrl":"10.1002/jcc.27511","url":null,"abstract":"Cisplatin (CDDP) is an effective Platinum (Pt) based anticancer drug used in chemotherapy. However, its effectiveness is limited due to its instability in solvents, along with the side effects it causes due to DNA damage. Nanoparticles (NPs) were developed in vitro to address these issues by loading CDDP into various types of NPs, including metal, lipid, and biological NPs. Citrate was employed as a biocompatible compound in nanomedicine to reduce cytotoxicity and enhance stability. In our study, the physicochemical and electronic properties of CDDP and citrate have been investigated using density functional theory (DFT), with a comparison of their behavior in water and DMSO. Additionally, TD-DFT was applied to analyze the UV–Vis spectra results. Six complexes have been proposed to better understand the interaction between citrate and CDDP. The results demonstrated that the CDDP could form stable complexes with citrate in both water and DMSO, and the considered complexes exhibited UV–Vis spectra within the experiment range. The frontier orbitals, electron densities mapping, and electrostatic potential analysis revealed that complex 5, where citrate di-substituted on two chlorides, is the most likely and effective complex. In summary, our investigation sheds light on the potential of CDDP-citrate complexes to address the limitations of CDDP, offering insights into their stability and interaction in solvents and highlighting the promising efficacy of specific complex formations for future therapeutic applications.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SeqDPI: A 1D-CNN approach for predicting binding affinity of kinase inhibitors

IF 3.4 3区化学

Journal of Computational Chemistry Pub Date : 2024-12-07 DOI: 10.1002/jcc.27518

Vinay Priy Mishra, Yogendra Narain Singh, Feroz Khan, Malay Kishore Dutta

{"title":"SeqDPI: A 1D-CNN approach for predicting binding affinity of kinase inhibitors","authors":"Vinay Priy Mishra, Yogendra Narain Singh, Feroz Khan, Malay Kishore Dutta","doi":"10.1002/jcc.27518","DOIUrl":"10.1002/jcc.27518","url":null,"abstract":"Predicting drug target binding affinity has huge relevance in Modern drug discovery and drug repositioning processes which assist doctors to come up with new drugs or even use the existing drugs for new target proteins. In silico models, using advanced deep learning techniques could further assist these prediction tasks by providing most prominent drug target pairs. Considering these factors, a deep learning based algorithmic framework is developed in this study to support drug target interaction prediction. The proposed SeqDPI model extract the relevant drug and protein features from the one dimensional Sequential representation of the dataset considered using optimized CNN networks that deploy convolutions on varying length of amino acid subsequence's to capture hidden pattern, the convolved drug- protein features obtained are then used as an input to L2 penalized feed forward neural network which matches the local residue patterns in protein classes with molecular fingerprints of drugs to predict the binding strength for all drug target pairs. The proposed model reduces the convolution strain typically encountered in existing in silico models that utilize complex 3D structures of drug protein datasets. The result shows that the SeqDPI model achieves a mean square error MSE of (0.167) across cross validation folds, outperforming baseline models such as KronRLS (0.406), Simboost (0.226), and DeepPS (0.214). Additionally, SeqDPI attains a high CI score of 0.9114 on the benchmark KIBA dataset, demonstrating its statistical significance and computational efficiency compared to existing methods. This gives the relevance and effectiveness of SeqDPI model in accurately predicting binding affinities while working with simpler one-dimensional data, making it a robust and computationally cost-effective solution for drug-target interaction prediction.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulating the oxygen affinity of porphyrins with metals, ligands, and functional groups: A DFT study

IF 3.4 3区化学

Journal of Computational Chemistry Pub Date : 2024-12-06 DOI: 10.1002/jcc.27505

Sebastian Ovalle, Cecile Malardier-Jugroot

{"title":"Modulating the oxygen affinity of porphyrins with metals, ligands, and functional groups: A DFT study","authors":"Sebastian Ovalle, Cecile Malardier-Jugroot","doi":"10.1002/jcc.27505","DOIUrl":"10.1002/jcc.27505","url":null,"abstract":"The interaction between different metals (M), axial ligands (L), and ring substituents (R) in porphyrins was investigated using density functional theory. Different combinations of iron and cobalt as metal centers; imidazole, chlorine, and an n-heterocyclic carbene (NHC) as axial ligands, and unsubstituted, octaethyl-, and tetraphenyl-porphyrins were explored in their low, intermediate, and high-spin states, alongside oxygen affinity. Remarkably, the n-heterocyclic carbene enhanced the affinity of cobalt porphyrins to oxygen, with binding energies on average 4.4 kcal mol−1 higher than FeP with the same ligand, and 0.78 kcal mol−1 higher than FeP with imidazole. The planarity of the iron tetraphenyl porphyrin with imidazole compared to its ruffled cobalt counterpart is noteworthy in both oxy- and deoxy-forms, highlighting imidazole's stabilizing influence on the porphyrin structure, particularly iron porphyrins, alongside imidazole's stabilizing effect on the affinity to O2. Despite the significant non-planarity induced by NHC as an axial ligand -regardless of the metal or ring substituent used-, it did not hinder the affinity of CoP to O2 (14.26 kcal mol−1, on average) as it did with the FeP with NHC (9.88 kcal mol−1, on average). Cobalt porphyrins with n-heterocyclic carbene ligands show promising potential for O2 activation or oxygen transport applications. The results show the complex interactions between the different parts of metalloporphyrins and highlight the capability of tailoring their affinity to O2. It also exemplifies the stabilizing effect of imidazole on the porphyrins, providing a very narrow range of binding energies and smaller differences in their geometries.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.27505","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Theoretical Study of the Subsequent Decomposition Mechanisms of 1,1-Diamino-2,2-dinitroethene (FOX-7)

IF 3.4 3区化学

Journal of Computational Chemistry Pub Date : 2024-12-05 DOI: 10.1002/jcc.27542

Yuheng Luo, Komal Yadav, Ralf Kaiser, Rui Sun

{"title":"Theoretical Study of the Subsequent Decomposition Mechanisms of 1,1-Diamino-2,2-dinitroethene (FOX-7)","authors":"Yuheng Luo, Komal Yadav, Ralf Kaiser, Rui Sun","doi":"10.1002/jcc.27542","DOIUrl":"10.1002/jcc.27542","url":null,"abstract":"<div>\u0000 \u0000 This computational study focuses on the mechanism of the consecutive decomposition of FOX-7 and compares the results with recent experimental study [J. Phys. Chem. A 2023, 127, 7707] under 202 nm photolysis (592 kJ/mol). The mechanisms of forming these compounds, including cyanamide variants (HNCNH and NH2CN), hydroxylamine (NH2OH), nitrosamine (NH2NO), diaminoacetylene (H2NCCNH2), cyanogen (NCCN), water (H2O), ammonia (NH3), urea ((NH2)2CO), hydroxyurea (NH2C(O)NHOH), and formamide (NH2CHO), have only been speculated on without any energetic information previously. This study employed an unsupervised potential energy profile search protocol and ab initio molecular dynamics (AIMD) simulations to identify reaction pathways leading to these compounds. The calculations reveal that although some products (e.g., HNCNH, NH2CN, H2NCCNH2, and NCCN) can be formed via unimolecular decomposition, other products (e.g., NH2OH, NH2NO, H2O, NH3, (NH2)2CO, NH2C(O)NHOH, and NH2CHO) are energetically favored if they are formed via bimolecular recombination between unimolecular decomposition products or a product and a FOX-7 molecule.\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142777402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Density Functional Theory (DFT) and Time-Dependent DFT (TDDFT) Studies of Porphyrin Adsorption on Graphene: Insights on the Effect of Substituents and Central Metal on Adsorption Energies

IF 3.4 3区化学

Journal of Computational Chemistry Pub Date : 2024-12-05 DOI: 10.1002/jcc.27526

Rayene Gara, Ángel Morales-García, Youssef Arfaoui, Francesc Illas

{"title":"Density Functional Theory (DFT) and Time-Dependent DFT (TDDFT) Studies of Porphyrin Adsorption on Graphene: Insights on the Effect of Substituents and Central Metal on Adsorption Energies","authors":"Rayene Gara, Ángel Morales-García, Youssef Arfaoui, Francesc Illas","doi":"10.1002/jcc.27526","DOIUrl":"10.1002/jcc.27526","url":null,"abstract":"Combining metalloporphyrins (MPr) and graphene constitutes key composites in the development of photovoltaic devices. Here, we focus on the analysis of the properties of metalloporphyrins/graphene systems by means of the density functional theory (DFT) and its time-dependent (TDDFT) version, focusing on the ground and singlet excited states. Our benchmark analysis concludes that ωB97XD density functional combined with 6-31G(d)/Def2-TZVP basis set is a better-suited method for simulating accurate MPr adsorption on graphene. It is shown that a reduced atomic model where the external organic shell of the structure is removed provides the same resulting optoelectronic properties of the original model, constituting an important speed-up of the calculations when studying porphyrins-derived molecules. We observe that ZnPr provides the highest light harvesting efficiency (LHE) value. In addition, we find out that the adsorption energy increases monotonically with the size of the graphene flake and the highest stability involves the use of graphene comprising above 500 atoms. Besides, CdPr and HgPr keep their properties as photosensitizers when they are bonded to graphene and show promising values in terms of LHE emerging as suitable solar energy harvesters.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.27526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142777452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-Walled ZnSe Nanotubes for High-Performance Photodetectors: A Computational Prediction

IF 3.4 3区化学

Journal of Computational Chemistry Pub Date : 2024-12-05 DOI: 10.1002/jcc.27539

Shuang Meng, Wenhui Li, Jia Zhou

引用次数: 0

Exploring the Possibility of a Planar Tetracoordinate Boron in BXY3 (X = B, Al, Ga; Y = C, Si, Ge) Clusters: A Theoretical Study

IF 3.4 3区化学

Journal of Computational Chemistry Pub Date : 2024-12-05 DOI: 10.1002/jcc.27525

Bhrigu Chakraborty, Pratim Kumar Chattaraj

{"title":"Exploring the Possibility of a Planar Tetracoordinate Boron in BXY3 (X = B, Al, Ga; Y = C, Si, Ge) Clusters: A Theoretical Study","authors":"Bhrigu Chakraborty, Pratim Kumar Chattaraj","doi":"10.1002/jcc.27525","DOIUrl":"10.1002/jcc.27525","url":null,"abstract":"<div>\u0000 \u0000 In this study, we investigated the potential energy surface of BXY3 (X = B, Al, Ga; Y = C, Si, Ge) clusters employing a few global optimization techniques. Remarkably, the global minimum structure obtained for most of the cases revealed a planar tetracoordinate boron atom, shedding light on the inherent stability of this motif. A comparative analysis of the performance of the different global optimization techniques employed is presented, offering insights into their efficacy. Additionally, the overall stability of the obtained global minimum structures is thoroughly examined through Atom-centered Density Matrix Propagation (ADMP) simulations spanning 20 ps at temperatures 300 and 500 K. The aromaticity of the respective clusters is also assessed via Nucleus Independent Chemical Shift (NICS) and Isochemical Shielding Surface (ICSS) calculations, providing valuable information regarding their electronic structure and stability. This comprehensive theoretical investigation contributes to our understanding of the structural properties of these clusters, with implications for their potential applications in various fields of chemistry.\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142777451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring Inhibition Mechanisms in Wildtype and T315I BCR-ABL1: An In Silico Approach Integrating Virtual Screening, MD Simulations, and MM-GBSA Analysis

IF 3.4 3区化学

Journal of Computational Chemistry Pub Date : 2024-12-05 DOI: 10.1002/jcc.27545

Ozlen Balta, Ercument Yilmaz, Gizem Tatar Yilmaz

{"title":"Exploring Inhibition Mechanisms in Wildtype and T315I BCR-ABL1: An In Silico Approach Integrating Virtual Screening, MD Simulations, and MM-GBSA Analysis","authors":"Ozlen Balta, Ercument Yilmaz, Gizem Tatar Yilmaz","doi":"10.1002/jcc.27545","DOIUrl":"10.1002/jcc.27545","url":null,"abstract":"<div>\u0000 \u0000 The BCR-ABL tyrosine kinase which is responsible for the pathogenesis of chronic myeloid leukemia (CML), has emerged as a promising therapeutic target. To address this issue, we employed a comprehensive computational approach integrating virtual screening, molecular dynamics (MD) simulations, and MM-GBSA (Molecular Mechanics/Generalized Born Surface Area) analysis to identify potential inhibitors and elucidate their binding mechanisms. Initially, virtual screening was conducted on 994 compounds from the ZINC database and, these compounds were docked against wildtype and T315I mutant ABL1 for the Type I and Type II ABL1 kinase inhibition mechanisms. In our molecular docking analysis for Type I inhibition, compound 911 demonstrated notable affinity towards the wildtype ABL1, with a binding energy of −14.91 kcal/mol, while compound 972 showed significant binding affinity towards the mutant ABL1, with a binding energy of −14.27 kcal/mol. In the Type II inhibition mechanism, the compounds with the highest binding affinity were compound 261 in wildtype ABL1 with −17.05 kcal/mol binding energy and compound 966 to the mutant ABL1 with a binding energy of −16.29 kcal/mol. Furthermore, analyses of MD simulations and MM/GBSA binding free energy (ΔG) were performed for target proteins with compounds, that exhibited the most favorable binding affinities with target proteins. The selected hit compounds showed ΔG scores ranging from −118.09 to −74.85 kJ/mol in both wildtype and mutant ABL1. Considering all in silico studies performed, it can be inferred that the identified molecules hold promise as potential candidates for drug design aimed at targeting CML.\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142777403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0