The Journal of Physical Chemistry B最新文献

{"title":"Constructing Predictive Implicit Solvent Models: Insights from Exploring Potential Parameter Space and Property Predictions.","authors":"Dan Zhang, Meng Deng, Chuncheng Li, Qinghua Ren, Zhaochuan Fan","doi":"10.1021/acs.jpcb.4c05190","DOIUrl":"10.1021/acs.jpcb.4c05190","url":null,"abstract":"<p><p>Implicit solvent (IS) models enhance the efficiency of simulating liquid systems, but those based on the potential of mean force calculations using explicit solvent (ES) models often fail to capture the solute structure and assembly dynamics under various conditions. This study examines the relationships between the parameter space of IS models and their predictive capabilities regarding solute structure and assembly dynamics, focusing on NaCl solutions and protein-bound silica colloidal nanoparticles. For NaCl solutions, models developed using concentration-dependent dielectric constants generally lack efficacy, and their effectiveness in predicting high-concentration liquid structures varies based on the ES model used. Adjusting the dielectric constant value or the shape of the short-range potentials can improve the accuracy of these models in predicting liquid structures. For protein-bound silica colloidal nanoparticles, we find that interaction site size and model resolution significantly influence the prediction of nanoparticle assembly dynamics, with different resolutions producing aggregates with distinct structures and connection modes. This study elucidates the complex relationship between parameter space in IS models and liquid structure and assembly kinetics, providing crucial insights for developing more accurate and predictive models.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12517-12532"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key Role of Cross-Linking Homogeneity in Polyurethane Mechanical Properties: Insights from Molecular Dynamics.","authors":"Chao Zhang, Yi Li, Yongshen Wu, Cuixia Wang, Jian Liang, Zihan Xu, Peng Zhao, Jing Wang","doi":"10.1021/acs.jpcb.4c05925","DOIUrl":"10.1021/acs.jpcb.4c05925","url":null,"abstract":"<p><p>Polyurethane (PU) grouting materials play a crucial role in trenchless rehabilitation with their mechanical properties significantly influenced by the cross-linking degree and cross-linking uniformity. This study investigates the effects of inhomogeneous cross-linking on the mechanical behavior of PU, an area that remains underexplored. We developed PU molecular models with varying cross-linking degrees and cross-linking uniformity, quantitatively described by the parameter <i>J</i>. A series-parallel spring network model was proposed to analyze their micromechanical responses under tensile stress. Our results indicate that cross-linking homogeneity, compared to the cross-linking degree, has a more significant impact on the mechanical properties of PU due to weaker parallel effects in specific series directions within the elastic network. Additionally, this defective network leads to larger free volume, stronger nonbonded interactions, smaller elastic variation, and weaker bonding contributions. Interestingly, this influence has an upper limit; under normal circumstances, <i>J</i> increases as the cross-linking degree increases. When <i>J</i> reaches a certain value, its effect diminishes, as indicated by the disappearance of network slippage during tensile testing. Therefore, PU with more uniform cross-linking exhibits a higher yield strength. These findings provide new insights into how cross-linking networks affect the mechanical properties of PU.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12612-12627"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Understanding of Superior Methylene Blue Adsorption Capacity in a Novel g-C₃N₄ Modified Amorphous Na-Ca-Mg Silicate Adsorbent: Insights from Multinuclear Solid-State NMR Spectroscopy.","authors":"Sezen Soyer-Uzun, Ping Yu, Feyza Kevser Öner, Sabyasachi Sen","doi":"10.1021/acs.jpcb.4c06514","DOIUrl":"10.1021/acs.jpcb.4c06514","url":null,"abstract":"<p><p>Silicate-based adsorbents offer significant advantages over traditional materials, particularly due to their superior thermal and chemical stability, enhanced regenerability, and the ability to endure more rigorous operating conditions. In this study, an amorphous Na-Ca-magnesium silicate adsorbent (SAAM) and its g-C₃N₄-modified counterpart (gCN-SAAM) were synthesized via alkali activation and a subsequent thermal process, respectively. The g-C₃N₄ modification resulted in a novel hybrid adsorbent with a remarkable methylene blue (MB) adsorption capacity of 420 mg g^-1, four times higher than the unmodified sample, setting a new benchmark. Solid-state ²⁹Si (MAS and CP/MAS), ¹H MAS, and ¹³C CP/MAS NMR spectroscopy were used to investigate the complex structures of these adsorbents and their interactions with MB. The local structure of SAAM primarily consists of Q³ Si units, with minor Q⁰ and Q¹ Si species, structural water, and Mg-OH sites. Exposure to MB caused an upfield shift in the ²⁹Si CP/MAS spectrum and enhanced resonances in the high-field region, indicating MB interaction with Si sites. ¹H MAS NMR spectra revealed significant interactions between water molecules in the geopolymer-like framework of SAAM and MB. The thermal treatment of SAAM with urea to produce gCN-SAAM enhanced the polymerization of Q³ Si species and increased the relative fraction of Q⁴ Si sites. This treatment also reduced the intensity of some Mg-OH units, showing interaction with g-C₃N₄. After MB adsorption on gCN-SAAM, NH₂ groups of g-C₃N₄ disappeared, and shifts in the C_2N-NHx and C_3N sites indicated their involvement in adsorption, while Si sites remained intact. This thermal method creates a sustainable, cost-effective and efficient adsorbent for MB removal from wastewater. Multinuclear NMR spectroscopy provides detailed insights into the adsorbent's complex structure and MB interactions, potentially guiding the design of improved future adsorbents.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12638-12650"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steric and Distance Effect on Electron Transfer in Dibenzo-Fused BODIPY-Based Photoredox Catalysts.","authors":"Sara Abuhadba, Neo Lin, Anthony Maltese, Michelle Ferek, Angela Chen, Charlotte Fuqua, Rilee Martzloff, Tomoyasu Mani, Tatiana V Esipova","doi":"10.1021/acs.jpcb.4c06886","DOIUrl":"10.1021/acs.jpcb.4c06886","url":null,"abstract":"<p><p>π-Extended BODIPY compounds are a compelling class of fluorophores known for their red or near-infrared (NIR) emission and high quantum yields, which are crucial for applications in materials science, solar cells, and biomedical imaging. Our recent study shows that we can use a dibenzo-fused BODIPY as a singlet-driven red photoredox catalyst by installing a simple electron donor group. Despite their potential in these applications, knowledge of electron transfer reactions involving dibenzo-fused BODIPY is still scarce. This paper presents the synthesis and systematic photophysical investigations of donor-acceptor (D-A) and donor-bridge-acceptor (D-bridge-A) series of dibenzo-fused BODIPY with <i>N</i>,<i>N</i>'-diethylaniline fragments serving as an electron donor. We examined the effects of methyl substituents and bridge length on the rates of photoinduced electron transfer (PeT). Through steady-state and time-resolved optical spectroscopy, electrochemistry, and density functional theory calculations, we elucidated how these simple structural modifications controlled the PeT rates and examined their impacts on catalytic activities in atom transfer radical addition (ATRA) reactions. Our results support previous studies on the (D-A) design of red heavy atom-free photocatalysts.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12549-12558"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying and Quantifying Borate Environments in Borosilicate Glasses: ¹¹B NMR-Peak Assignments Assisted by Double-Quantum Experiments.","authors":"Baltzar Stevensson, Peng Lv, Mattias Edén","doi":"10.1021/acs.jpcb.4c06721","DOIUrl":"10.1021/acs.jpcb.4c06721","url":null,"abstract":"<p><p>We discuss the prospects for accurate ¹¹B magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) spectral deconvolutions for reaching beyond the readily extracted borate speciations offered by the integrated resonances of the coexisting B^[3] and B^[4] species of the respective BO₃ and BO₄ network groups in borosilicate (BS) glasses. We critically review hitherto proposed ¹¹B^[3] and ¹¹B^[4] NMR-peak assignments relating to their neighboring Si, B^[3] and B^[4] species, as quantified by MAS NMR spectral deconvolution. Guidance to these resonance assignments was offered from double-quantum-single-quantum (2Q-1Q) ¹¹B MAS NMR experiments that inform about the B^[<i>p</i>]-O-B^[<i>q</i>] network linkages. The NMR spectral deconvolutions from two BS glass series with low nonbridging oxygen (NBO) contents and fixed molar ratios <i>n</i>_Si/<i>n</i>_B = {1.0, 2.0} but variable network-modifying cations of alkali metals and Mg²⁺ revealed a dominance of B^[4]-O-Si linkages, yet with a significant dependence on the BO₃ population of the glass, which was rationalized by the different propensities for B^[4]-O-{Si, B^[3], B^[4]} linkage formation. For BS glasses with comparable B and Si contents, we recommend three-peak deconvolutions of the ¹¹B^[4] spectral region, whose ¹¹B^[4](<i>m</i>Si) sites differ in their (average) numbers of <i>m</i> B^[4]-O-Si and 4 - <i>m</i> B^[4]-O-B^[<i>p</i>] bonds, where B^[<i>p</i>] may assume B^[3] <i>or</i> B^[4]. We also discuss the structural origin of the two rather arbitrarily classified \"ring\" and \"non-ring\" B^[3] entities, where 2Q-1Q ¹¹B NMR suggests the former to primarily constitute BO₃ groups that coexist with BO₄ moieties in (superstructural) ring units largely devoid of bonds to Si, whereas the \"non-ring\" B^[3] sites involve linkages to all of B^[3], B^[4], and Si, with B^[3]-O-Si linkages prevailing. The limitations of ¹¹B NMR spectral deconvolutions are discussed, including the remaining challenges in analyzing NBO-rich BS glasses.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12651-12667"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Origin of Automatic Rhodopsin Modeling Outliers Using the Microbial <i>Gloeobacter</i> Rhodopsin as Testbed.","authors":"Darío Barreiro-Lage, Vincent Ledentu, Jacopo D'Ascenzi, Miquel Huix-Rotllant, Nicolas Ferré","doi":"10.1021/acs.jpcb.4c05962","DOIUrl":"10.1021/acs.jpcb.4c05962","url":null,"abstract":"<p><p>The automatic rhodopsin modeling (ARM) approach is a computational workflow devised for the automatic buildup of hybrid quantum mechanics/molecular mechanics (QM/MM) models of wild-type rhodopsins and mutants, with the purpose of establishing trends in their photophysical and photochemical properties. Despite the success of ARM in accurately describing the visible light absorption maxima of many rhodopsins, for a few cases, called outliers, it might lead to large deviations with respect to experiments. Applying ARM to<i>Gloeobacter</i> rhodopsin (GR), a microbial rhodopsin with important applications in optogenetics, we analyze the origin of such outliers in the absorption energies obtained for GR wild-type and mutants at neutral pH, with a total root-mean-square deviation (RMSD) of 0.42 eV with respect to the experimental GR excitation energies. Having discussed the importance and the uncertainty of one particular amino-acid p<i>K</i>_a, namely histidine at position 87, we propose and test several modifications to the standard ARM protocol: (i) improved p<i>K</i>_a predictions along with the consideration of several protonation microstates, (ii) attenuation of the opsin electrostatic potential at short-range, (iii) substitution of the state-average complete active space (CAS) electronic structure method by its state-specific approach, and (iv) complete replacement of CAS with mixed-reference spin-flip time-dependent density functional theory (MRSF-TDDFT). The best RMSD result we obtain is 0.2 eV combining the protonation of H87 and using MRSF/CAMH-B3LYP.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12368-12378"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the Catalytic Potential of Anionic Micelles: Insights into the Ce(IV)-Directed Phenylalanine Oxidation Kinetics in Asymmetric Hydrophobic Environments.","authors":"Priya Karmakar, Mousumi Layek, Sk Mehebub Rahaman, Sandip Kundu, Kripasindhu Karmakar, Arnab Patra, Ujjwal Mandal, Pintu Sar, Bidyut Saha","doi":"10.1021/acs.jpcb.4c06663","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06663","url":null,"abstract":"<p><p>The oxidation kinetics of phenylalanine (Phe) by Ce(IV) have been examined in both the absence and presence of aqueous micellar media with asymmetric tails, specifically using sodium dodecyl sulfate (SDS) and sodium tetradecyl sulfate (STS) surfactants. The reaction progress was monitored by observing a decrease in absorbance using UV-vis spectroscopy. Interestingly, the kinetic profile revealed a consistent increase in the observed rate constant values as the concentration of the surfactant increased. The kinetic results have been analyzed by using numerous experimental studies, such as dynamic light scattering (DLS), zeta potential, ¹H NMR analysis, FT-IR spectroscopy, conductometry, scanning electron microscopy (SEM), fluorometry, time-correlated single-photon counting (TCSPC), and transmission electron microscopy (TEM). Micellar aggregates maintain their spherical shape in the presence of the substrate, even at higher surfactant concentrations, as revealed by microstructural analysis. The substrate molecules are encapsulated to a greater extent in the inner micellar core of STS micelles on account of the more hydrophobic nature of STS surfactants. Therefore, in STS micellar media, fewer substrate molecules diffuse to the Stern layer compared to the SDS micellar medium, resulting in fewer molecules participating in the oxidative transformation reaction. As a result, the rate enhancement of oxidation kinetics is less pronounced in STS micelles than in SDS micelles. A plausible mechanism that aligns with the kinetic results has been highlighted, along with the interpretation of the Piszkiewicz model, to explain the observed catalytic effect of both micellar mediums.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theoretical Mechanism of Rh-Containing Species Catalyzing the Hydrogenolysis of Lignin Model Compounds Using -C_αO-H and -C_α-H Groups as Superior H-Sources.","authors":"Han-Yun Min, Jin-Shan Xiong, Ting-Hao Liu, Jin-Tao Gou, Chang-Wei Hu, Hua-Qing Yang","doi":"10.1021/acs.jpcb.4c06298","DOIUrl":"10.1021/acs.jpcb.4c06298","url":null,"abstract":"<p><p>The hydrogenolysis of lignin model compounds (MCs) into high-value chemicals has received increasing attention, but their catalytic reaction mechanisms are not yet very clear. Here, we report the reaction mechanisms of the hydrogenolysis of MC into 4-acetylanisole (AAL) and guaiacol (GAL) catalyzed by LRuCl₃ (L = 4'-(4-methoxyphenyl)-2,2':6',2″-terpyridine) with MC, H₂, and 1-phenylethan-1-ol (PEO) as the H-sources in aqueous solution with the Bro̷nsted base (NaOH), at the M06/def2-TZVP, 6-311++G (d,p) theoretical level, namely, RS-Self, RS-H₂, and RS-PEO, respectively. After dissociation in NaOH aqueous solution, the LRuCl₃ compound can form a stable complex LRh (OH)₃ as the initial catalytically active species. Their rate-determining steps are related to the cleavage of the -C_αO-H bond in both RS-Self-and RS-PEO, whereas it is associated with the heterolysis of the H-H bond in RS-H₂. From NaOH aqueous solution, the OH^- ligand of LRh(OH)₃ promotes the cleavage of the -C_αO-H bond with MC and PEO as H-sources, whereas it advances the heterolysis of the H-H bond with H₂ as the H-source, owing to its strong Bro̷nsted basicity. Furthermore, the Rh center of LRh(OH)₃ mediates the cleavage of the -C_α-H bond, because of its Lewis acidity. The reaction activity lowers as RS-Self > RS-PEO ≫ RS-H₂, which is positively dependent on the protonation degree of the departing H atom. Compounds containing both -C_αO-H and -C_α-H groups can act as effective donors for H-sources. In the meantime, the stronger the electron-withdrawing groups they contain, the more pronounced the protonation of the -C_αO-H group and the higher the reaction activity in providing H-sources. The present results provide insights into utilizing lignin's own functional groups as a hydrogen source for high-value conversion.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12540-12548"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"All-Atom Perspective of the DENV-3 Methyltransferase Inhibition Mechanism.","authors":"Xiao Liu, Kaiwen Pang, Hangfei Wu, Xiaohui Wang, John Z H Zhang, Zhaoxi Sun","doi":"10.1021/acs.jpcb.4c05943","DOIUrl":"10.1021/acs.jpcb.4c05943","url":null,"abstract":"<p><p>The Dengue virus (DENV) is an enveloped, single-stranded RNA virus with several antigenically distinct serotypes (DENV-1 to DENV-5). Dengue fever, as a major public health threat transmitted by mosquitoes, affects millions of people worldwide (especially in tropical and subtropical regions). Toward drug developments of DENV, the nonstructural protein 5 methyltransferase (MTase) serves as an attractive target. The MTase transforms <i>S</i>-adenosyl methionine to <i>S</i>-adenosyl homocysteine (SAH), which is thereby selected as the target with which external drugs compete with. In this work, using alanine scanning with generalized Born and interaction entropy (ASGB-IE), we provide an all-atom perspective of the protein-ligand interactions formed by DENV-3 MTase and SAH derivatives. Residues with consistently high contributions to stabilization are summarized, and the general DENV-3 MTase inhibition mechanism is elucidated. Additionally, the mutational impact on binding thermodynamics is found to be entropy-driven. We also highlight the advantage of the ASGB-IE method for affinity estimation compared to standard end-point protocols, which is highly related to the selection of interfacial residues in free energy estimation. Finally, we performed a thorough scan of the mutational space on critical sites (saturation mutagenesis) and identified 14 mutants causing resistance to the current inhibitors.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12358-12367"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organophosphate Hydrolysis by a Designed Metalloenzyme: Impact of Mutations Explained.","authors":"Edyta Dyguda-Kazimierowicz, Wiktoria Jedwabny","doi":"10.1021/acs.jpcb.4c06809","DOIUrl":"10.1021/acs.jpcb.4c06809","url":null,"abstract":"<p><p>The efficient design of novel enzymes has been attainable only by a combination of theoretical approaches and experimental refinement, suggesting inadequate performance of de novo design protocols. Based on the analysis of the evolutionary trajectory of a designed organophosphate hydrolase, this work aimed at developing and validating the improved theoretical models describing the catalytic activity of five enzyme variants (including wild-type as well as theoretically derived and experimentally refined enzymes) performing the hydrolysis of diethyl 7-hydroxycoumarinyl phosphate. The following aspects possibly important for enzyme design were addressed: the level of theory sufficient for a reliable description of enzyme-reactant interactions, the issue of ground state (GS) destabilization versus transition state (TS) stabilization, and the derivation of the proper side chain rotamers of amino acid residues. For enzyme variants analyzed herein, differential transition state stabilization (DTSS, i.e., preferential TS binding by an enzyme over the GS binding) calculated with a non-empirical model of the interaction energy (i.e., multipole electrostatic plus approximate dispersion terms, MED) displayed a superior performance in ranking the enzyme catalytic activity. The MED DTSS-based systematic rotamer refinement performed with an efficient scanning procedure and accounting for long-range interaction energy terms is an important step capable of unlocking the full potential impact of the given residue that could be otherwise overlooked with a conventional static approach featuring optimization to the nearby minimum. While TS stabilization is the main factor contributing to the increased catalytic activity of the de novo-designed variant studied in this work, directed evolution refinement appears to impact the catalytic activity of another enzyme variant analyzed herein via GS destabilization.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12456-12470"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}