Journal of Molecular Modeling最新文献

Context

Molecular docking is vital for structure-based virtual screening and heavily depends on accurate and robust scoring functions. Scoring functions often inadequately account for the breakage of solvent hydrogen bonds, hindering the accuracy of predicting binding energy. Here, we introduce LeScore, a novel scoring function that specifically incorporates the hydrogen bonding penalty (HBP) in an aqueous environment, aiming to penalize unfavorable polar interactions when hydrogen bonds with water are broken but the energy loss is not fully compensated by newly formed protein–ligand interactions. LeScore was optimized for descriptor combinations and subsequently validated using a testing data set, achieving a Pearson correlation coefficient (rp) of 0.53 in the training set and 0.52 in the testing set. To evaluate its screening capability, a subset of the Directory of Useful Decoys: Enhanced (DUD-E) was used. And LeScore achieved an AUC of 0.71 for specific targets, outperforming models without HBP and enhancing the ranking and classification of active compounds. Overall, LeScore provides a robust tool for improving virtual screening, especially in cases where hydrogen bonding is crucial for ligand binding.

Method

LeScore is formulated as a linear combination of descriptors, including van der Waals interactions, hydrogen bond energy, ligand strain energy, and newly integrated HBP. The function was optimized using multiple linear regression (MLR) on the PDBbind 2019 dataset. Evaluation metrics, such as Pearson and Spearman correlation coefficients were utilized to assess the performance of 12 descriptor combinations. Additionally, the study employed datasets from the DUD-E to evaluate LeScore’s ability to distinguish active ligands from decoys across multiple target proteins.

Context

Anthracycline anticancer antibiotics from Streptomyces peucetius show high affinity for nucleobases. This study uses quantum mechanical density functional theory (DFT) to investigate interactions between doxorubicin (DOX) tautomers and the guanine-cytosine (GC) base pair. Intermolecular distances and interaction energies reveal structural relationships and stabilization. Interaction energy studies show that DOX-GC has greater binding affinity and greater stability in the aqueous phase as compared to that in gaseous phase. Interestingly, the tautomer which show greater affinity for GC in the gas phase is different from the one in the aqueous phase. Reduced density gradient (RDG) scatter plots and quantum theory of atoms in molecules (QTAIM) confirm the presence of hydrogen bonds and its strength. Natural bond orbital (NBO) analysis elucidates donor–acceptor orbital interactions. These findings provide an understanding of the intermolecular interactions between DOX tautomers and the GC base pair, which is likely to provide insight into the molecular basis for DOX’s anticancer activity and therapeutic efficacy.

Methods

DFT calculations were performed using the B3LYP functional with a 6-31G(d,p) basis set in the Gaussian 09 package, including solvent effects through the integral equation formalism polarizable continuum model (IEF-PCM). Topological analysis and quantum theory of atoms in molecules (QTAIM) studies were conducted using the Multiwfn program, while non-covalent interactions were analysed using visual molecular dynamics (VMD) software.

Graphical Abstract

Context

This research focuses on the theoretical study of six push–pull molecules composed of conjugated bridges based on porphyrin and metalloporphyrins where the metals used are Fe(II), Co(II), Ni(II), Cu(II), and Zn(II); these bridges are linked at their ends by acceptor groups (–NO₂) and donors (–N(CH₃)₂) at the meso positions of the cycles mentioned before. The CAM–B3LYP, M08HX, and MN15 functionals tend to describe well the systems studied in non-linear optics NLO in addition to the use of the basis set 6–31 +  + G(d,p) which is considered to be the adequate and least expensive basis set. The highest values of the first static hyperpolarizabilities (β_tot) are assigned to the two molecules 2A and 3A; the corresponding values are as follows: β_tot (2A) = 46.43 * 10⁻³⁰ esu and β_tot (3A) = 46.30 * 10⁻³⁰ esu. The highest value of the second static hyperpolarizability (γ_av) is assigned to the molecule 1A5 with a value of 9.49 * 10⁻³⁵ esu. The highest values of the first dynamic hyperpolarizabilities (({beta }_||^{lambda }(-2omega ;omega ,omega ))) and second dynamics hyperpolarizabilities (({gamma }_||^{lambda }(-2omega ;omega ,omega ,0))) are attributed to the molecule 2A; the corresponding values are as follows:({beta }_||^{lambda }(-2omega ;omega ,omega ))) (2A) = 8229.88 * 10⁻³⁰ esu and ({gamma }_||^{lambda }(-2omega ;omega ,omega ,0)) (2A) =  − 10,943.10 * 10⁻³⁵ esu. The molecules 1A2 and 1A5 based on the metals Co(II) and Zn(II), respectively, are the most profitable in second- and third-order dynamic NLOs. The specific solvents for the six molecules are acetone, acetonitrile, and dichloromethane. The maximum wavelengths recorded for all molecules in vacuum and in combination with all solvents are in the range 355.75 to 397.15 nm and absorb in the UV transparency.

Method

All calculations were performed with the Gaussian 16 program. The dispersion functional B3LYP–D3 is used for optimizations. Electronic parameters were calculated using the following functionals: CAM-B3LYP, LC-wPBE, LC-BLYP, M11, wB97X, M08-HX, M06-2X, MN12SX, and MN15. The basis set studied for the whole manuscript is 6–31 +  + G(d,p) for non-metallic atoms and LanL2DZ for transition metals. Other basis sets studied include 6–31G(d,p), 6–31 +  + G(d,p), cc–pVDZ, AUG–cc–pVDZ, 6–311G(d,p), 6–311 +  + G(d,p), cc–pVTZ, and AUG–cc–pVTZ. The natural bond orbital (NBO) method was also considered. The implicit solvation models studied are solvation models based on density (SMD) and conductor polarizable continuum model (C–PCM). The time-dependent density functional (TD-DFT) approach was also studied.

Graphical Abstract

Context

This article suggests that the olfaction process can be simplified to an adsorption mechanism by utilizing the Machilis hrabei olfactory receptor MhOR5 as a biological adsorbent. The odorant molecules such as geosmin, linalool, and o-cresol were used as adsorbates. The aim of the present study is to provide new insights into the docking process of the tested odorants on MhOR5 using numerical simulation via an advanced statistical physics model to fit the corresponding response curves.

Methods

In the present work, an advanced theory based on statistical physics formalism is applied to understand and analyze the experimental dose-olfactory response curves of three odorant molecules on the Machilis hrabei olfactory receptor. Indeed, a monolayer model with four energy levels developed using the grand canonical ensemble was successfully applied to analyze the adsorption mechanism of geosmin, linalool, and o-cresol on MhOR5 through the interpretation of the different fitted parameters. Stereographically, it was found that geosmin, linalool, and o-cresol molecules were docked on MhOR5 binding pockets with nonparallel orientations (multi-molecular process) since all the numbers of the studied odorants adsorbed on one binding pocket were superior to 1. Energetically, the values of the molar adsorption energies ΔE_i (i = 1, 2, 3, and 4) related to the four types of binding pockets (varied between 6.18 and 18.43 kJ/mol) demonstrated that the three odorants were exothermically and physically docked on MhOR5 since all values of ΔE_i were positive and inferior to 40 kJ/mol. The proposed model may also be applied to calculate and interpret two thermodynamic potentials: the internal energy E_int and adsorption entropy S_a. Additionally, the physicochemical parameters may be used to stereographically and energetically characterize the heterogeneity of the insect MhOR5 surface. The docking simulation results demonstrated that the estimated binding affinities or energy score values (varied between 6.27 and 18.40 kJ/mol) were slightly similar to molar adsorption energy values and were included in the adsorption energy bands of the three adsorption energy distributions (AEDs).

Context

Zinc sulfide (ZnS) and (zinc telluride (ZnTe) are binary semiconductor compounds that exhibit excellent optical and electrical properties, and the mechanical behavior at the nanoscale level is crucial for their potential application. Nevertheless, experimental data are scarce regarding the mechanical characteristics of ZnS and ZnTe. For better applications of ZnS and ZnTe-based devices, it is crucial to understand, design, and control their mechanical properties. In this work, we have examined the indentation on (001), (110), and (111) planes of ZnS and ZnTe at the nanometric scale, along with an exploration of the associated plastic deformation utilizing molecular dynamics techniques. We compared and analyzed the loading curves, dislocation distribution evolutions, atomic displacement vectors, and stress distributions of the two materials under indentation.

Method

The indentation simulations were performed in molecular dynamics software LAMMPS, using the Stillinger–Weber potential model. Visual analysis is done using OVITO software. A spherical indenter with a diameter of 12.0 nm moves down to the substrates for a depth of 5.0 nm at a steady speed of 0.01 nm/ps. Distinct anisotropic characteristics can be detected from the loading forces, dislocation distributions, atomic displacement vectors, and stress distributions. The dislocation distributions exhibit fourfold, twofold, and threefold symmetries in the case of (001), (110), and (111) planes. Results indicate that stress underneath the indenter should prompt the atoms to move, subsequently leading to the formation, propagation, and distribution of the dislocations. Another notable characteristic is the emergence of prismatic loops in ZnS. The findings offering valuable data for future utilization considerations.

Context

Methyl formate (MF) has been detected in several interstellar environments, but whether or not the formation of this molecule takes place in the gas phase or on the ices of interstellar grains is still unclear. In this study, we explore the synthesis of methyl formate through the nucleophilic acyl substitution (S(_{text {N}})Acyl) reaction between methanol (CH(_{3})OH) and formic acid (HCOOH) on amorphous solid water, which is the main component of interstellar ice mantles.

Methods

Using density functional theory (DFT), we model MF formation by sampling HCOOH in different catalytic sites on the water clusters with CH(_{3})OH, and vice versa, for initial reactant configurations. We select the initial binding modes from the binding energy distributions of both reactant species. We assess the energy and synchronicity of the reaction by analyzing the reaction mechanisms through intrinsic reaction coordinate (IRC) energy, reaction force, and reaction electronic flux profiles. Using Wiberg bond order derivatives, we identify reaction events linked to hidden transition states that are encountered along the reaction coordinate.

Context

Membrane separation technology is a great candidate for capturing and separating CO₂ from air and flue gas, aiming at combating global warming. In particular, numerous experimental and theoretical investigations have revealed the outstanding performance of porous graphene membrane in sieving CO₂ due to its high-selectivity and energy-efficiency. Some experimental studies have confirmed that the graphene can be spontaneously contaminated by the hydrocarbons in ambient air, due to its large surface energy. However, how the covered hydrocarbons on porous graphene membrane affect the CO₂ capture and separation remains elusive. In this study, we employed molecular dynamics (MD) simulation approach to investigate CO₂/N₂ separation capacity of the oleophobic N24 nanopores and the oleophilic C24 nanopores in graphene membrane after covering the oleaginous hydrocarbon, C₈H₁₈, films. Interestingly, our MD simulations demonstrate that the oleophobic N24 nanopore shows higher CO₂ transport rate and CO₂/N₂ selectivity compared with the oleophilic C24 nanopore after the membrane adsorbed by C₈H₁₈ films, indicating that the oleophobic N24 graphene nanopore can ameliorate CO₂ capture and separation upon C₈H₁₈ films adsorption. Mechanically, on the one hand, C₈H₁₈ can more likely block the C24 nanopore, due to the stronger affinity of C₈H₁₈ to the C24 pore, which results in the reduced gas transport rate. On the other hand, the quadrupole interaction between CO₂ and N24 nanopore helps the favorable capture and separation of CO₂ by N24 nanopore. The combined effect thus determines the better CO₂ separation performance of hydrocarbon covered N24 nanopore. Therefore, our findings not only reveal the carbon capture and separation performance of porous graphene membrane upon spontaneously adsorbing hydrocarbon from the ambient air or the flue gas for the first time, but also exploit the oleophobic nanopore capable of ameliorating the membrane capacity, which is beneficial to future practical application of porous graphene membrane in CO₂ separation.

Methods

We conducted all MD simulations with GROMACS software package. VMD software package was used to visualizing the simulation conformations and trajectories. Periodic boundary conditions were applied in all directions (x, y, and z). Temperature was constrained at 350 K using the v-rescale thermostat. Long-range electrostatic interactions were computed using the PME method, and van der Waals (vdW) interactions were calculated with a cutoff distance of 12 Å. Bonds involving hydrogen atoms were constrained to their equilibrium values using the LINCS algorithm. 

Context

Nitrous acid (HONO) is often associated with many air pollution events, such as the ozone hole, acid rain, and human health. Herein, we performed the theoretical studies on the structures and enthalpy of formation for the hydrated clusters HONO∙(H₂O)_n(n = 1–7). Two different isomers of HONO including cis-HONO and trans-HONO were studied. Minima structures of trans-HONO∙(H₂O)_n(n = 1–7) and cis-HONO∙(H₂O)_n(n = 1–7) clusters containing forty-eight and twenty-one were found, respectively. The hydrogen-bonded interactions between HONO and water molecules in HONO∙(H₂O)_n(n = 1–7) clusters were analyzed. Enthalpies of the formation of the most stable isomers of trans-HONO∙(H₂O)_n(n = 1–7) and cis-HONO∙(H₂O)_n(n = 1–7) clusters are predicted theoretically. These results can provide a new understanding of the atmospheric circulation of HONO.

Methods

Geometric structures and vibrational frequencies of the HONO∙(H₂O)_n(n = 1–7) clusters were investigated by using the QCISD(T)/6–311 + G(3df,2p)//M06-2X/6–311 + G(3df,2p) method. Enthalpies of formation of the global minimal isomers of the HONO∙(H₂O)_n(n = 1–7) clusters were calculated at the CBS-QB3 level of theory. Atoms in molecules (AIM) theory was applied to the analysis of hydrogen-bonded interactions among the HONO∙(H₂O)_n(n = 1–7) clusters.

Context

Interactions between proteins and RNA, as well as between their structural fragments, are widespread in biological objects. We obtained the optimized structures of complexes of the glutathione anion with neutral molecules of uracil, thymine and cytosine. It was established that all complexes are stabilized by hydrogen bonds. The preference for various H-donors in nucleic base molecules (HN(1) or HN(3) in uracyl and thymine, N(1) or H2N in cytosine) for hydrogen bonding with the peptide has been analyzed. Chain elongation from dipeptide to tripeptide creates favorable conditions for increasing the number of hydrogen bonds in the complex. The strongest hydrogen bonds are formed with the carboxylate group of the peptide. Energy advantage of complexation with cytosine compared to other pyrimidine bases, and advantage of complexation with thymine compared to uracil have been established. The contributions of structural rearrangement of molecules, intermolecular interactions and H-bonding to the total values ​​of potential energy and Gibbs energy of the complexation process have been discussed.

Methods

The article combines the results of calculations by the DFT/ B97D/6–311 + + G(3d,3p) and QTAIM methods to model the structure of ion-molecular complexes between the tripolar anion of peptide (glutathione) and neutral nucleic bases (uracil, thymine, cytosine). The PCM was used for solvent (water). Conformational analysis of the glutathione molecule was performed by scanning the potential energy while varying the dihedral angles. Several initial structure of peptide – nucleic base complexes with different modes of coordination were created in accordance with the MEP results. Non-covalent specific interactions in the complex were highlighted by RDG analysis. The hydrogen bond energies in complexes were calculated based on the correlation with the electron density at bond critical points. Changes in the total energy and Gibbs energy during complex formation, as well as contributions ​​from intermolecular interactions and structural rearrangement of reagent molecules, were determined.

Context

This research determined the crystal structure, molecular structure, electronic structure, optical properties, mechanical properties, and Hirshfeld analysis of the CL-20/4,5-MDNI cocrystal at two distinct stoichiometric ratios under hydrostatic pressures varying from 0 to 100 GPa. The findings revealed that the CL-20/4,5-MDNI cocrystal with a 1:1 ratio experienced two structural transitions at pressures of 80 GPa and 90 GPa. Notably, new covalent bonds, C10-O13 and C9-O14, were established, whereas the C10-H10C bond was disrupted. In contrast, the CL-20/4,5-MDNI cocrystal with a 1:3 ratio underwent three structural transformations at pressures of 55 GPa, 63 GPa, and 95 GPa, leading to the creation of new covalent bonds such as C17-N35, C25-N43, C14-O9, C21-O7, and N27-H9. These transitions were corroborated through the examination of lattice parameters, variations in covalent bond lengths, density of states, and optical coefficients. Additionally, the study explored the similarities and differences between the two cocrystals in terms of their crystal structure, molecular structure, electronic properties, optical properties, mechanical properties, and Hirshfeld analysis.

Method

In this investigation, the CASTEP module from the Materials Studio software package was utilized to perform first-principles calculations based on density functional theory (DFT). Specifically, the Broyden–Fletcher–Goldfarb–Shanno (BFGS) optimization technique was applied to refine the geometric structures of the CL-20/4,5-MDNI cocrystals, which were prepared in the stoichiometric ratios of 1:1 and 1:3. These calculations were conducted under a range of hydrostatic pressures, varying from 0 to 100 GPa. To achieve a fully relaxed state at atmospheric pressure, the Perdew–Zunger local density approximation (LDA/CA-PZ) functional was employed. The plane wave cutoff energy was meticulously set at 489 eV to ensure the convergence of the total energy within the unit cell system. Additionally, the k-point mesh was configured as 1 × 1 × 1 to facilitate accurate calculations. Before each simulation, different hydrostatic pressures were systematically applied to analyze the structural changes under varying conditions.