Journal of Computational Chemistry最新文献

{"title":"An ANI-2 enabled open-source protocol to estimate ligand strain after docking","authors":"Francois Berenger, Koji Tsuda","doi":"10.1002/jcc.27478","DOIUrl":"https://doi.org/10.1002/jcc.27478","url":null,"abstract":"In protein-ligand docking, the score assigned to a protein-ligand complex is approximate. Especially, the internal energy of the ligand is difficult to compute precisely using a molecular mechanics based force-field, introducing significant noise in the rank-ordering of ligands. We propose an open-source protocol (https://github.com/UnixJunkie/MMO), using two quantum mechanics (QM) single point energy calculations, plus a Monte Carlo (Monte Carlo) based ligand minimization procedure in-between, to estimate ligand strain after docking. The MC simulation uses the ANI-2x (QM approximating) force field and is performed in the dihedral space. On some protein targets, using strain filtering after docking allows to significantly improve hit rates. We performed a structure-based virtual screening campaign on nine protein targets from the Laboratoire d'Innovation Thérapeutique—PubChem assays dataset using Cambridge crystallographic data centre genetic optimization for ligand docking. Then, docked ligands were submitted to the strain estimation protocol and the impact on hit rate was analyzed. As for docking, the method does not always work. However, if sufficient active and inactive molecules are known for a given protein target, its efficiency can be evaluated.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"54 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377462","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}

{"title":"Fluxional halogen bonds in linear complexes of tetrafluorodiiodobenzene with dinitrobenzene.","authors":"Cai-Yue Gao, Bin-Bin Pei, Si-Dian Li","doi":"10.1002/jcc.27483","DOIUrl":"https://doi.org/10.1002/jcc.27483","url":null,"abstract":"<p><p>The fluxional nature of halogen bonds (XBs) in small molecular clusters, supramolecules, and molecular crystals has received considerable attention in recent years. In this work, based on extensive density-functional theory calculations and detailed electrostatic potential (ESP), natural bonding orbital (NBO), non-covalent interactions-reduced density gradient (NCI-RDG), and quantum theory of atoms in molecules (QTAIM) analyses, we unveil the existence of fluxional halogen bonds (FXBs) in a series of linear (IC₆F₄I)_m(OONC₆H₄NOO)_n (m + n = 2-5) complexes of tetrafluorodiiodobenzene with dinitrobenzene which appear to be similar to the previously reported fluxional hydrogen bonds (FHBs) in small water clusters (H₂O)_n (n = 2-6). The obtained <math> <semantics><mrow><mi>GS</mi> <mo>⇌</mo> <mi>TS</mi> <mo>⇌</mo> <msup><mi>GS</mi> <mo>'</mo></msup> </mrow> <annotation>$$ mathrm{GS}rightleftharpoons mathrm{TS}rightleftharpoons {mathrm{GS}}^{hbox{'}} $$</annotation></semantics> </math> fluxional mechanisms involve one FXB in the systems which fluctuates reversibly between two linear CI···O XBs in the ground states (GS and GS') via a bifurcated CI  O₂N van der Waals interaction in the transition state (TS). The cohesive energies (E_coh) of these complexes with up to four XBs exhibit an almost perfect linear relationship with the numbers of XBs in the systems, with the average calculated halogen bond energy of E_coh/XB = 3.48 kcal·mol^-1 in the ground states which appears to be about 55% of the average calculated hydrogen bond energy (E_coh/HB = 6.28 kcal·mol^-1) in small water clusters.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337873","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}

{"title":"Theoretical design of new ligands to boost reaction rate and selectivity in palladium-catalyzed aromatic fluorination.","authors":"Josefredo R Pliego","doi":"10.1002/jcc.27513","DOIUrl":"https://doi.org/10.1002/jcc.27513","url":null,"abstract":"<p><p>The development of palladium-catalyzed fluorination with biaryl monophosphine ligands has faced two important problems that limit its application for bromoarenes: the formation of regioisomers and insufficient catalysis for heteroaryl substrates as bromothiophene derivatives. Overcoming these problems requires more ligand design. In this work, reliable theoretical calculations were used to elucidate important ligand features necessary for achieving more rate acceleration and selectivity. These features include increasing the ligand-substrate repulsion and creating a negative charge in the space around the fluoride ion bonded to the palladium. The investigated L5 ligand presents these features, and the calculations predict that this ligand completely suppresses the regioisomer formation in the difficult case of 4-bromoanisole. In addition, the free energy barriers are decreased by 2-3 kcal mol^-1 in comparison with the catalysis involving the AlPhos ligand. Thus, the present study points out a direction for new developments in palladium-catalyzed fluorination.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337874","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}

{"title":"Hydride and halide abstraction reactions behind the enhanced basicity of Be and Mg clusters with nitrogen bases","authors":"Manuel Yáñez, Otilia Mó, M. Merced Montero-Campillo, Ibon Alkorta, José Elguero","doi":"10.1002/jcc.27509","DOIUrl":"https://doi.org/10.1002/jcc.27509","url":null,"abstract":"In this study, we investigate the protonation effects on the structure, relative stability and basicity of complexes formed by the interaction of monomers and dimers of BeX₂ and MgX₂ (X = H, F) with NH₃, CH₂NH, HCN, and NC₅H₅ bases. Calculations were performed using the M06-2X/aug-cc-pVTZ formalism, along with QTAIM, ELF and NCI methods for electron density analysis and MBIE and LMO-EDA energy decomposition analyses for interaction enthalpies. The protonation of the MH₂– and M₂H₄–Base complexes occurs at the negatively charged hydrogen atoms of the MH₂ and M₂H₄ moieties through typical hydride abstraction reactions, while protonation at the N atom of the base is systematically less exothermic. The preference for the hydride transfer mechanism is directly associated with the significant exothermicity of H₂ formation through the interaction between H⁻ and H⁺, and the high hydride donor ability of these complexes. The basicity of both, MH₂ and M₂H₄ compounds increases enormously upon association with the corresponding bases, with the increase exceeding 40 orders of magnitude in terms of ionization constants. Due to the smaller exothermicity of HF formation, the basicity of fluorides is lower than that of hydrides. In Be complexes, the protonation at the N atom of the base dominates over the fluoride abstraction mechanism. However, for the Mg complexes the fluoride abstraction mechanism is energetically the most favorable process, reflecting the greater facility of Mg complexes to lose F⁻.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"36 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329121","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}

{"title":"Theoretical study on the luminescent and reaction mechanism of dansyl-based fluorescence probe for detecting hydrogen sulfide.","authors":"Huixue Li,Yvhua Wang,Sujuan Pan,Changqing Wang,Yanzhi Liu,Kun Yuan,Lingling Lv,Zhifeng Li","doi":"10.1002/jcc.27506","DOIUrl":"https://doi.org/10.1002/jcc.27506","url":null,"abstract":"The photophysical and photochemical properties of the sulfonyl azide-based fluorescent probe DNS-Az and its reduction product DNS by hydrogen sulfide (H2S) have been investigated theoretically. The calculated results indicated the first excited states of DNS-Az was dark state (oscillator strength less than 0.03) and DNS was bright state (oscillator strength more than 0.1), which determined the predicted radiative rate kr of DNS-Az was much smaller than that of DNS, meanwhile, due to more larger reorganization energy of DNS-Az, its predicted internal conversion rate kic was four times larger than that of DNS; moreover, owing to the effect of heavy atom from sulfur atom in DNS-Az, its predicted intersystem crossing rate kisc was seven times larger than that of DNS, thus the calculated fluorescence quantum yield of DNS-Az was only 2.16% and that of DNS was more than 77.2%, the above factors is the basis for DNS-Az molecule to function as a fluorescent probe. Regarding both DNS-Az and DNS molecules, their maximum Huang-Rhys factors, which are less than unity, signify the reliability of 0-0 transitions between their S0 and S1 electronic states. In addition, for DNS, our simulated emission peak of the 0-0 transition is 515 nm, a value that exhibits enhanced accuracy and coherence when compared to the experimental datum of 528 nm. The reaction mechanism of DNS-Az generating DNS by H2S has been investigated too, according to the potential energy profile, we found that the fluorescent probe firstly protonated, then this organic ion broke down into DNS with the aid of a proton.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"55 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324880","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}

{"title":"Development of a machine learning-based target-specific scoring function for structure-based binding affinity prediction for human dihydroorotate dehydrogenase inhibitors","authors":"Jinhui Meng, Li Zhang, Zhe He, Mengfeng Hu, Jinhan Liu, Wenzhuo Bao, Qifeng Tian, Huawei Feng, Hongsheng Liu","doi":"10.1002/jcc.27510","DOIUrl":"https://doi.org/10.1002/jcc.27510","url":null,"abstract":"Human dihydroorotate dehydrogenase (hDHODH) is a flavin mononucleotide-dependent enzyme that can limit de novo pyrimidine synthesis, making it a therapeutic target for diseases such as autoimmune disorders and cancer. In this study, using the docking structures of complexes generated by AutoDock Vina, we integrate interaction features and ligand features, and employ support vector regression to develop a target-specific scoring function for hDHODH (TSSF-hDHODH). The Pearson correlation coefficient values of TSSF-hDHODH in the cross-validation and external validation are 0.86 and 0.74, respectively, both of which are far superior to those of classic scoring function AutoDock Vina and random forest (RF) based generic scoring function RF-Score. TSSF-hDHODH is further used for the virtual screening of potential inhibitors in the FDA-Approved &amp; Pharmacopeia Drug Library. In conjunction with the results from molecular dynamics simulations, crizotinib is identified as a candidate for subsequent structural optimization. This study can be useful for the discovery of hDHODH inhibitors and the development of scoring functions for additional targets.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"30 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321880","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}

{"title":"Facile heterolytic bond splitting of molecular chlorine upon reactions with Lewis bases: Comparison with ICl and I2","authors":"Anna V. Pomogaeva, Anna S. Lisovenko, Alexey Y. Timoshkin","doi":"10.1002/jcc.27507","DOIUrl":"https://doi.org/10.1002/jcc.27507","url":null,"abstract":"Formation of molecular complexes and subsequent heterolytic halogen‐halogen bond splitting upon reactions of molecular Cl<jats:sub>2</jats:sub> with nitrogen‐containing Lewis bases (LB) are computationally studied at M06‐2X/def2‐TZVPD and for selected compounds at CCSD(T)/aug‐cc‐pvtz//CCSD/aug‐cc‐pvtz levels of theory. Obtained results are compared with data for ICl and I<jats:sub>2</jats:sub> molecules. Reaction pathways indicate, that in case of Cl<jats:sub>2</jats:sub>∙LB complexes the activation energies for the heterolytic Cl‐Cl bond splitting are lower than the activation energies of the homolytic splitting of Cl<jats:sub>2</jats:sub> molecule into chlorine radicals. The heterolytic halogen splitting of molecular complexes of X<jats:sub>2</jats:sub>∙Py with formation of [XPy<jats:sub>2</jats:sub>]<jats:sup>+</jats:sup>… contact ion pairs in the gas phase is slightly endothermic in case of Cl<jats:sub>2</jats:sub> and I<jats:sub>2</jats:sub>, but slightly exothermic in the case of ICl. Formation of {[ClPy<jats:sub>2</jats:sub>]<jats:sup>+</jats:sup>…}<jats:sub>2</jats:sub> dimers makes the overall process exothermic. Taking into account that polar solvents favor ionic species, generation of donor‐stabilized Cl<jats:sup>+</jats:sup> in the presence of the Lewis bases is expected to be favorable. Thus, in polar solvents the oxidation pathway via donor‐stabilized Cl<jats:sup>+</jats:sup> species is viable alternative to the homolytic Cl‐Cl bond breaking.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"96 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276744","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}

{"title":"Modeling the effect of substituents on the electronically excited states of indole derivatives","authors":"Jordan Howe, Salsabil Abou-Hatab, Spiridoula Matsika","doi":"10.1002/jcc.27502","DOIUrl":"https://doi.org/10.1002/jcc.27502","url":null,"abstract":"A proper understanding of excited state properties of indole derivatives can lead to rational design of efficient fluorescent probes. The optically active &lt;span data-altimg=\"/cms/asset/02f49cd1-0816-4191-bf02-eab476d6678a/jcc27502-math-0001.png\"&gt;&lt;/span&gt;&lt;mjx-container ctxtmenu_counter=\"2\" ctxtmenu_oldtabindex=\"1\" jax=\"CHTML\" role=\"application\" sre-explorer- style=\"font-size: 103%; position: relative;\" tabindex=\"0\"&gt;&lt;mjx-math aria-hidden=\"true\" location=\"graphic/jcc27502-math-0001.png\"&gt;&lt;mjx-semantics&gt;&lt;mjx-mrow&gt;&lt;mjx-msub data-semantic-children=\"0,1\" data-semantic- data-semantic-role=\"latinletter\" data-semantic-speech=\"upper L Subscript a\" data-semantic-type=\"subscript\"&gt;&lt;mjx-mrow&gt;&lt;mjx-mi data-semantic-annotation=\"clearspeak:simple\" data-semantic-font=\"italic\" data-semantic- data-semantic-parent=\"2\" data-semantic-role=\"latinletter\" data-semantic-type=\"identifier\"&gt;&lt;mjx-c&gt;&lt;/mjx-c&gt;&lt;/mjx-mi&gt;&lt;/mjx-mrow&gt;&lt;mjx-script style=\"vertical-align: -0.15em;\"&gt;&lt;mjx-mrow size=\"s\"&gt;&lt;mjx-mi data-semantic-annotation=\"clearspeak:simple\" data-semantic-font=\"italic\" data-semantic- data-semantic-parent=\"2\" data-semantic-role=\"latinletter\" data-semantic-type=\"identifier\"&gt;&lt;mjx-c&gt;&lt;/mjx-c&gt;&lt;/mjx-mi&gt;&lt;/mjx-mrow&gt;&lt;/mjx-script&gt;&lt;/mjx-msub&gt;&lt;/mjx-mrow&gt;&lt;/mjx-semantics&gt;&lt;/mjx-math&gt;&lt;mjx-assistive-mml display=\"inline\" unselectable=\"on\"&gt;&lt;math altimg=\"urn:x-wiley:01928651:media:jcc27502:jcc27502-math-0001\" display=\"inline\" location=\"graphic/jcc27502-math-0001.png\" overflow=\"scroll\" xmlns=\"http://www.w3.org/1998/Math/MathML\"&gt;&lt;semantics&gt;&lt;mrow&gt;&lt;msub data-semantic-=\"\" data-semantic-children=\"0,1\" data-semantic-role=\"latinletter\" data-semantic-speech=\"upper L Subscript a\" data-semantic-type=\"subscript\"&gt;&lt;mrow&gt;&lt;mi data-semantic-=\"\" data-semantic-annotation=\"clearspeak:simple\" data-semantic-font=\"italic\" data-semantic-parent=\"2\" data-semantic-role=\"latinletter\" data-semantic-type=\"identifier\"&gt;L&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mi data-semantic-=\"\" data-semantic-annotation=\"clearspeak:simple\" data-semantic-font=\"italic\" data-semantic-parent=\"2\" data-semantic-role=\"latinletter\" data-semantic-type=\"identifier\"&gt;a&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;$$ {L}_a $$&lt;/annotation&gt;&lt;/semantics&gt;&lt;/math&gt;&lt;/mjx-assistive-mml&gt;&lt;/mjx-container&gt; and &lt;span data-altimg=\"/cms/asset/c9728526-a064-4f11-aaa8-0e51ea044cad/jcc27502-math-0002.png\"&gt;&lt;/span&gt;&lt;mjx-container ctxtmenu_counter=\"3\" ctxtmenu_oldtabindex=\"1\" jax=\"CHTML\" role=\"application\" sre-explorer- style=\"font-size: 103%; position: relative;\" tabindex=\"0\"&gt;&lt;mjx-math aria-hidden=\"true\" location=\"graphic/jcc27502-math-0002.png\"&gt;&lt;mjx-semantics&gt;&lt;mjx-mrow&gt;&lt;mjx-msub data-semantic-children=\"0,1\" data-semantic- data-semantic-role=\"latinletter\" data-semantic-speech=\"upper L Subscript b\" data-semantic-type=\"subscript\"&gt;&lt;mjx-mrow&gt;&lt;mjx-mi data-semantic-annotation=\"clearspeak:simple\" data-semantic-font=\"italic\" data-semantic- data-semantic-parent=\"2\" data-semantic-role=\"latinletter\" data-semantic-type=\"identifier\"&gt;&lt;mjx-c&gt;&lt;/mjx-c&gt;&lt;/mjx-mi&gt;&lt;/mjx-mrow&gt;&lt;mjx-script style=\"vertical-align: -0.15em;\"&gt;&lt;mjx-mrow size=\"s\"&gt;&lt;mjx-mi","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"7 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247221","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}

{"title":"Efficient acceleration of the convergence of the minimum free energy path via a path-planning generated initial guess","authors":"Yi Sun","doi":"10.1002/jcc.27504","DOIUrl":"https://doi.org/10.1002/jcc.27504","url":null,"abstract":"We demonstrate that combining a shifted clustering algorithm with a fast-marching-based algorithm can generate accurate approximations of the minimum energy path (MEP) given a free energy landscape (FEL). Using this approximation as the initial guess for the MEP, followed by further refinement with the string method (referred to as the fast marching tree (FMT)-string combined approach), significantly reduces the number of iterations required for MEP convergence. This approach saves substantial time compared to using linear interpolation (LI) for the initial guess. Our method offers a viable solution for obtaining an effective initial guess of the MEP when an approximate or converged FEL is available. This work highlights the potential of applying FMT-based approaches to extract the MEP in chemical reactions.","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"15 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142237228","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}

{"title":"An influence of electronic structure theory method, thermodynamic and implicit solvation corrections on the organic carbonates conformational and binding energies","authors":"Alexander S. Ryzhako,&nbsp;Anna A. Tuma,&nbsp;Arseniy A. Otlyotov,&nbsp;Yury Minenkov","doi":"10.1002/jcc.27471","DOIUrl":"10.1002/jcc.27471","url":null,"abstract":"<p>An impact of an electronic structure or force field method, gas-phase thermodynamic correction, and continuum solvation model on organic carbonate clusters (S)_<i>n</i> conformational and binding energies is explored. None of the tested force field (GFN-FF, GAFF, MMFF94) and standard semiempirical methods (PM3, AM1, RM1, PM6, PM6-D3, PM6-D3H4, PM7) can reproduce reference RI-SCS-MP2 conformational energies. Tight-binding GFN<i>n</i>-xTB methods provide more realistic conformational energies which are accurate enough to discard the least stable conformers. The effect of thermodynamic correction is moderate and can be ignored if the gas phase conformational stability ranking is a goal. The influence of continuum solvation is stronger, especially if reinforced with the Gibbs free energy thermodynamic correction, and results in the reduced spread of conformational energies. The cluster formation binding energies strongly depend on a particular approach to vibrational thermochemistry with the difference between traditional harmonic and modified scaled rigid – harmonic oscillator approximations reaching 10 kcal mol⁻¹.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"45 32","pages":"3004-3016"},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236699","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}