Molecular Dynamics Simulation Method Research Articles

Novel α-glucosidase Inhibitors Designed as Type 2 Diabetes Drugs by QSAR, Molecular Docking and Molecular Dynamics Simulation Methods.

Diabetes mellitus is a globally prevalent disease of significant concern. Alpha-glucosidase has emerged as a prominent target for the treatment of type 2 diabetes. In this study, 39 α-glucosidase inhibitors (AGIs) of tetrahydrobenzo[b]thiophene-2-ylurea derivatives to establish a stable and valid Topomer CoMFA model, with a cross-validation coefficient (q²) of 0.766 and a non-cross-validation coefficient (r²) of 0.960. Subsequently, the ZINC15 database was used to screen the fragments, based on which 13 novel inhibitor molecules with theoretically potentially high activity were designed. Molecular docking and molecular dynamics simulations to understand the binding status of the inhibitor molecules to the target proteins showed that amino acids ASP215, GLN279 and ARG442 may form hydrogen bonds with the ligands and therefore enhance the inhibitory effect of the small molecules. Additionally, MM/PBSA calculations suggest that the newly designed molecules demonstrate more stable binding modes, and these newly designed molecules showed good ADMET properties with potential as AGIs. The findings would provide valuable guidance and a theoretical foundation for the design and development of novel AGIs.

Molecular dynamics simulation of nanocellulose and cement matrix composites

The interfacial properties of nanocellulose and cement matrix are the key factors affecting the mechanical properties of composite materials. However, it is challenging to study the interface combination through conventional experiments and microscopic characterization techniques. Molecular dynamics simulation (MD), as a nanoscale analytical method, can be used to calculate and analyze the strength, deformation, destruction and interfacial interaction of materials on the atomic scale. Since the existing methods of C-S-H modeling and fiber pull-out from the matrix in molecular dynamics simulations were not suitable for cellulose/C-S-H composite models. In this paper, a molecular dynamics simulation method for nanocellulose cement matrix composites was proposed. Based on the embedded composite model, the tensile stress-strain, interfacial interaction energy, hydrogen bond, and interface failure mode were studied when cellulose was pulled out of the matrix. The results showed that adding cellulose could improve the local ductility and tensile strength of cement matrix materials. The interfacial interaction energy between cellulose and C-S-H was approximately −1.09 J/m2, which was much higher than that between carbon nanotubes and C-S-H. Cellulose would adsorb hydrogen and oxygen atoms on H2O, OH− and silica tetrahedron in C-S-H. In the pull-out simulation of cellulose in C-S-H, C-S-H on the surface of cellulose would be destroyed and attached to the cellulose surface and moved along with it, indicating that cellulose could play a good bridging role in the matrix. The simulation results revealed the action mechanism of cellulose in cement matrix materials.

Implementing reactivity in molecular dynamics simulations with harmonic force fields

The simulation of chemical reactions and mechanical properties including failure from atoms to the micrometer scale remains a longstanding challenge in chemistry and materials science. Bottlenecks include computational feasibility, reliability, and cost. We introduce a method for reactive molecular dynamics simulations using a clean replacement of non-reactive classical harmonic bond potentials with reactive, energy-conserving Morse potentials, called the Reactive INTERFACE Force Field (IFF-R). IFF-R is compatible with force fields for organic and inorganic compounds such as IFF, CHARMM, PCFF, OPLS-AA, and AMBER. Bond dissociation is enabled by three interpretable Morse parameters per bond type and zero energy upon disconnect. Use cases for bond breaking in molecules, failure of polymers, carbon nanostructures, proteins, composite materials, and metals are shown. The simulation of bond forming reactions is included via template-based methods. IFF-R maintains the accuracy of the corresponding non-reactive force fields and is about 30 times faster than prior reactive simulation methods.

Functionalized Amorphous Carbon Materials via Reactive Molecular Dynamics Simulations.

We derive a database of atomistic structural models of amorphous carbon materials endowed with exohedral functional groups. We start from phases previously derived using the DynReaxMas method for reactive molecular dynamics simulations, which exhibit atomistic and medium-length-scale features in excellent agreement with available experimental data. Given a generic input structure/phase, we develop postprocessing simulation algorithms mimicking experimental preparation protocols aimed at: (1) "curing" the phase to decrease the defect concentration; (2) automatically selecting the most reactive carbon atoms via interaction with a probe molecular species, and (3) stabilizing the phase by saturating the valence of carbon atoms with single-bond functional groups. Although we focus on oxygen-bearing functionalities, they can be replaced with other monovalent groups, such as -H, -COOH, -CHO, so that the protocol is quite general. We finally classify reactive sites in terms of their location within the structural framework and coordination environment (edges, tunnels, rings, aromatic carbons becoming aliphatic) and try to single out descriptors that correlate with tendency to functionalization.

Exploring TβRI inhibitors from Arenaria kansuensis based on 3D-QSAR, molecular docking and molecular dynamics simulation methods and its anti-pulmonary fibrosis molecular mechanism validation

Ethnopharmacological relevancePulmonary fibrosis (PF) is a kind of interstitial lung disease that seriously threatens human life and health. Up to now, there is no specifically therapeutic drug. Arenaria kansuensis, a typical Tibetan medicine, has been previously proved to have anti-PF pharmacological activity by our group. However, the specific target and molecular mechanism of pharmacological active ingredients from it are still unknown. Aim of the studyThis study aimed to explore the molecular mechanism and specific target of pharmacological active ingredients from A. kansuensis for treating PF. Materials and methodsVirtual screening including 3D-QSAR, molecular docking and molecular dynamics simulation were used to screen TβRI inhibitor. CETSA experiment was used to verify the interaction between GAK (a β-carboline alkaloid isolated from A. kansuensis) and TβRI. Cell and molecular experiments including observation of cell morphology and Western blot were applied to investigate the molecular mechanism of action of GAK for treating PF. Animal experiments including physiological index, immunohistochemistry and ELISA were used to comprehensively evaluate the anti-PF effect of GAK and explore the corresponding mechanism of action. ResultsResults of 3D-QSAR experiment indicated that GAK is a much stronger potential TβRI inhibitor, molecular mechanism study showed that 30 μM GAK could significantly keep TβRI more stable which indicated that the direct binding interaction between GAK and TβRI, it targetedly inhibited TβRI through forming hydrogen bonds with LYS232, SER280 and ASP351 and the binding energies is −56.05 kcal/mol.In vitro experiment showed GAK could suppress downstream signal pathways of TβRI including MAPK, PI3K/AKT and NF-κB pathways during EMT process. In vivo experiment showed that GAK could improve the survival rate and body weight of PF mice, alleviate the symptoms of histopathological severity, inflammatory cell infiltration and collagen deposition in lung tissue of PF mice through inhibiting EMT process of PF. ConclusionsThis work not only provided evidence to support GAK as a novel TβRI inhibitor for treating PF through multiple pathways, but also reveal the specific target and molecular mechanism of β-carboline alkaloids from A. kansuensis for treating PF.

Investigating the Effect of Chemical Modifications on the Ribose Sugar Conformation, Watson-Crick Base Pairing, and Intrastrand Stacking Interactions: A Theoretical Approach.

Over the last few decades, chemically modified sugars have been incorporated into nucleic acid-based therapeutics to improve their pharmacological potential. Chemical modification can influence the sugar conformation, Watson-Crick hydrogen (W-C) bonding, and nucleobase stacking interactions, which play major roles in the structural integrity and dynamic properties of nucleic acid duplexes. In this study, we categorized 33 uridine (U*) and cytidine (C*) sugar modifications and calculated their sugar conformational parameters. We also calculated the Watson-Crick hydrogen bond energies of the modified RNA-type base pairs (U*:A and C*:G) using DFT and sSAPT0 methods. The W-C base pairing energy calculations suggested that the South-type modified sugar strengthens the C*:G base pair and weakens the U*:A base pair compared to the unmodified one. In contrast, the North-type sugar modifications form weaker C*:G base pair and marginally stronger U*:A base pair compared to the South-type modified sugars. Moreover, intrastrand base stacking energies were calculated for 15 modifications incorporated at the fourth position in 7-mer non-self-complementary RNA duplexes [(GCAU*GAC)2 and (GCAC*GAC)2], utilizing molecular dynamics simulation and quantum mechanical (DFT and sSAPT0) methods. The sugar modifications were found to have minimal effect on the intrastrand base-stacking interactions. However, the glycol nucleic acid modification disturbs the intrastrand base-stacking significantly, corroborating the experimental data.

Molecular dynamics simulation on de-icing behavior of nanodroplets on amorphous SiO2

Abstract The ice formation and detachment process of nanoscale water droplets on the amorphous SiO2 substrate, which is for simulating the glass of solar panels, is studied in this paper by molecular dynamics simulation methods, considering the effects of environmental temperature, onset of icing time, and parameters of the nanoarray on the ice formation morphology and ice adhesion strength. The results show that the ice adhesion strength is independent of the environmental temperature. The time of icing onset influences the recoil state of droplets, with a larger spreading area leading to higher adhesion strength. The increase in height and decrease in width of the nanocolumns of nanoarray structure leads to an increase in the contact angle of the droplet, causing a reduction in ice adhesion strength, albeit with a slight rise within a certain height range.

Phase diagram for nanodroplet impact on solid spheres: From hydrophilic to superhydrophobic surfaces

The impact of droplets on solid surfaces is a crucial fluid phenomenon in the additive industry, biotechnology, and chemistry, where controlling impact dynamics and duration is essential. While extensive research has focused on flat substrates, our understanding of impact dynamics on curved surfaces remains limited. This study seeks to establish phase diagrams for the process of droplet impact on solid spheres and further quantitatively describe the effect of curvature through theoretical analysis. It aims to determine the critical conditions between different impact outcomes and also establish a scaling relationship for the contact time. Here, the post-impact outcome regimes occurring for a wide range of Weber numbers (We) from 1.2 to 173.8, diameter ratio (λ) of solid spheres to nanodroplets from 0.25 to 2, and surface wettability (θ) from 21° to 160°, through the molecular dynamics simulation method (MD) and theoretical analysis. The MD simulations reveal that the phase diagrams of droplet impacts on hydrophilic, hydrophobic, and superhydrophobic spheres differ, with specific distinctions focusing on rebound and three different forms of dripping. Furthermore, a theoretical model based on the principle of energy conservation during impact on superhydrophobic surfaces has been developed to predict the critical conditions between rebound and dripping states, showing good agreement with simulation results. Additionally, a new scaling relationship of contact time for droplet impact on superhydrophobic spherical surfaces has also been established by extending and modifying the existing models, which also agrees well with the simulated results. These insights provide a foundational understanding for designing surface structures.

Study on the Factors Affecting the Self-Healing Performance of Graphene-Modified Asphalt Based on Molecular Dynamics Simulation.

To comprehensively understand the impact of various environmental factors on the self-healing process of graphene-modified asphalt, this study employs molecular dynamics simulation methods to investigate the effects of aging degree (unaged, short-term aged, long-term aged), asphalt type (base asphalt, graphene-modified asphalt), healing temperature (20 °C, 25 °C, 30 °C), and damage degree (5 Å, 10 Å, 15 Å) on the self-healing performance of asphalt. The validity of the established asphalt molecular models was verified based on four physical quantities: density, radial distribution function analysis, glass transition temperature, and cohesive energy density. The simulated healing time for the asphalt crack model was set to 200 ps. The following conclusions were drawn based on the changes in density, mean square displacement, and diffusion coefficient during the simulated healing process under different influencing factors: Dehydrogenation and oxidation of asphalt molecules during the aging process hinder molecular migration within the asphalt crack model, resulting in poorer self-healing performance. As the service life increases, the decline in the healing performance of graphene-modified asphalt is slower than that of base asphalt, indicating that graphene-modified asphalt has stronger anti-aging properties. When the vacuum layer in the asphalt crack model is small, the changes in the diffusion coefficient are less pronounced. As the crack width increases, the influence of various factors on the diffusion coefficient of the asphalt crack model becomes more significant. When the crack width is large, the self-healing effect of asphalt is more dependent on these influencing factors. Damage degree and oxidative aging have a more significant impact on the healing ability of graphene-modified asphalt than healing temperature.

Interface dynamics in dewatering processes of high-water-content slurry flocculated with PAC

This study addresses the challenge of the reverse effect observed in the dewatering process of waste slurry as poly-aluminum chloride (PAC) dosages increase. It investigates the flocculation mechanism of PAC at varying dosages in a high-water-content slurry using molecular dynamics simulation methods. The results indicate that PAC molecules primarily adsorb montmorillonite particles while exerting negligible influence on quartz. Dewatering efficiency is influenced by the adsorption-repulsion interaction at the PAC-montmorillonite interface. Efficiency increases with PAC dosage up to an optimum level due to enhanced adsorption but decreases thereafter due to increasing repulsion. Within this optimal range, montmorillonite interfaces exhibit a higher negative charge, facilitating stable PAC adsorption and leading to increased aggregation of montmorillonite particles, thereby forming flocs. The adsorption capacity of PAC on montmorillonite particles escalates with dosage until achieving the optimal flocculation effect. However, surpassing this optimal dosage prompts repulsion among outer PAC molecules, gradually causing montmorillonite particles to separate due to repulsion, thereby weakening the flocculation effect. This research provides theoretical support for the flocculation and dewatering of PAC in high-water-content waste slurry, emphasizing the rational and cost-effective addition of PAC in practical applications.

Binding Mechanism of Nitro Musks to Human Lactoferrin: Multispectral Approach, Docking and Molecular Dynamics Simulation.

Nitro musks are highly bioaccumulative and potentially carcinogenic, commonly used as additives in fabric softeners, detergents, and other household products. Furthermore, these substances have been detected in breast milk and human adipose tissue, posing a risk of direct exposure to pregnant women and infants. Human lactoferrin (HLF) is abundant in colostrum, and plays an important role in the non-specific immune system of the human body. In this study, the mechanisms of action of two nitro musk compounds, typical examples of synthetic musks, with HLF were investigated using molecular docking, dynamics simulation and multispectral methods. The fluorescence findings demonstrated that nitro musks quenched the intrinsic fluorescence of human lactoferrin through static quenching. Thermodynamic analysis of the binding parameters suggested that hydrophobic interactions acted synergistically in the formation of the complex. Moreover, analyses utilizing multispectral techniques, such as Fourier transform infrared (FTIR) spectroscopy, validated that the microenvironment and structure of HLF were altered in the presence of nitro musks. Finally, molecular docking and molecular dynamics simulations were employed to explore the specific binding mode of nitro musks with HLF and to assess the stability of the complex. These findings may provide a reference for assessing health risks to pregnant women and infants.

Exploring Novel Quinoline-1,3,4-Oxadiazole Derivatives for Alzheimer's Disease: Their Design, Synthesis, and In-Vitro and In-Silico Investigations.

Alzheimer's Disease (AD) is a complicated and advanced neurodegenerative condition accompanied by gradual cholinergic neuronal death and higher levels of monoamine oxidase-B (MAO-B) enzyme. In this study, a series of novel hybrid compounds combining 1,3,4-oxadiazole and quinoline moieties were synthesized and evaluated for their potential as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and MAO enzymes. The chemical structures of the synthesized compounds were confirmed using various analytical techniques, such as mass spectrometry, infrared spectroscopy (IR), proton nuclear magnetic resonance (1H-NMR), and carbon and nuclear magnetic resonance (13C-NMR). The final products were evaluated for anticholinesterase potential by applying modified Ellman's spectrometric method, whereas a fluorometric method was used to assess MAO inhibition properties. In-silico studies using molecular docking and molecular dynamics simulation (MDS) methods has been also conducted. Among the synthesized compounds, 5a, 5c, and 6a demonstrated substantial activity against AChE, with IC50 values of 0.033 μM, 0.096 μM, and 0.177 μM, respectively. A molecular docking study was performed to elucidate the binding modes and establish the structure-activity relationship (SAR) of the most active compounds (5a, 5c, and 6a). Molecular dynamics simulation (MDS) of the most potent compound, 5a, was also conducted to examine the stability of the interactions with the receptor. Moreover, the physicochemical properties of the active products were also studied. Overall, this research contributes to the development of 1,3,4-oxadiazole- quinoline hybrids as potential AChE inhibitors for the treatment of Alzheimer's disease.

Effect of chitooligosaccharide on the binding domain of the SARS-COV-2 receptor

The receptor-binding domain (RBD) is crucial for understanding how severe acute respiratory syndrome coronavirus (SARS-CoV-2) recognizes and infects host cells. Chitooligosaccharide (CS) exhibits diverse antiviral activities, with its derivatives showing remarkable efficacy in blocking SARS-CoV-2 infection. Thus, this study employed spectroscopy, virus-infected cell experiments, and molecular simulation to investigate the molecular interactions between CS and SARS-CoV-2 RBD, as well as their mechanisms. In spectroscopic experiments, all four CS variants with different molecular weights formed interactions with the RBD. These variants increased the resistance of HEK293ACE2 cells to SARS-CoV-2 invasion. Molecular docking revealed that the four CS variants could bind to the RBD through hydrogen bonding or salt-bridge interactions, forming stable complexes. Chitotetraose provided stronger protection to HEK293ACE2 cells compared to other CS variants and displayed higher molecular docking scores. Further investigation into the optimal docking conformation of chitotetraose was conducted through molecular dynamics simulation methods. This study lays a solid theoretical foundation and provides a scientific basis for the development of targeted RBD inhibitors, as well as drug screening and application against novel coronaviruses.

Molecular dynamics simulation on the variations in characteristics of aqueous solution with diverse additives: Inspirations for binary ice preparation

Ice slurry, as a novel energy storage medium, possesses the superiority of high energy storage density. The freezing point inhibitors are employed to regulate the supercooling phenomenon of water, while the macroscopic experiments are complicated to elucidate the action mechanism. Consequently, this paper adopts molecular dynamic simulation method to investigate the mean square displacement, radial distribution function, hydrogen bonds types, hydrogen bonds number and length of water at various concentrations of ethanol, NaCl, and SiO2 additives. The results indicate that the average number of hydrogen bonds of the system composed with 600 pure water molecules is 1127.24, and the average length of hydrogen bonds is 2.33 Å. Moreover, the addition of alcoholics and chlorides inhibits the hydrogen bonds between water and water molecules, and promotes the generation of hydrogen bonds, thus weakening the diffusion motion of water molecules. Whereas, it is observed that the addition of nanoparticles leads to agglomeration in pure water system, resulting an increase in the viscosity and a decrease in the diffusion rate of the system. The proposed microscopic model can effectively depict the potential interaction mechanisms of additives and water, which is contributing to develop effective freezing point inhibitors and improve the energy utilization efficiency.

Molecular interactions of the antioxidant in the coolant oil for energy transformers: Dielectric and simulation studies

This research paper presents experimental and theoretical findings concerning the blending of mineral oil and vegetable oils, both with and without antioxidants. The study analyses a variety of parameters for different blends of mineral and vegetable oils, including breakdown voltage, ageing resistance, dielectric constant, viscosity, dissipation factor, surface tension, flash point, and fire point. The study was further extended to investigate the effects of varying the amount of antioxidants added to mineral oil blends with different vegetable oils. The best transformer insulating solution is found by extensive analyses that include measurements of breakdown voltage, flash point, fire point, and surface tension. This blends’ properties with antioxidant are either better than pure mineral oil or comparable to mineral oil. Density functional theory (DFT) analyses the molecular structure and dipole moment of an antioxidant. Molecular dynamics simulation method (MD) analysis of the average water residual time – periods of an antioxidant will show the stability of H-bond interactions. The primary objective of this experiment is to unveil a novel liquid-insulating material that not only excels in dielectric performance but also aligns with environmentally friendly practices.

Effect of UEVC parameters on cutting surface quality and subsurface damage of single crystal γ-TiAl alloy via atomic simulation

TiAl alloys are favored by the aerospace industry due to its excellent mechanical properties. However, its intrinsic brittleness, the use of conventional cutting (CC) process leads to the problems of high cutting force and high cutting temperature, which in turn affects the machined surface quality. Ultrasonic elliptical vibratory cutting (UEVC) has been proved to be an effective method to improve the surface quality and reduce the subsurface damage of difficult-to-machine materials. This paper compares the effects of CC and UEVC processes on cutting forces and subsurface damage based on molecular dynamics simulation methods, and the effects of elliptical vibration frequencies and amplitude ratios (AR) on surface morphology, roughness, and subsurface damage are investigated. The results show that the cutting force and subsurface damage in the UEVC process are reduced compared with that in the CC. Due to the vibration frequency, the subsurface damage is mainly dominated by atomic clusters, and both surface and subsurface masses show an optimization trend as the vibration frequency decreases. In terms of the AR, the surface quality is better at an AR of 2/3, with less activation of immovable dislocations, and the degree of subsurface damage decreases as the AR increases, and a relatively stable defective structure emerges when the AR is 1/2. The simulation results facilitate an atomic-scale comprehension of the removal mechanism of UEVC and further provide a theoretical foundation for the surface mass and subsurface damage mechanism and optimization of vibrational parameters of UEVC single crystal γ-TiAl alloy.

How specific ion effects influence the mechanical behaviors of amide macromolecules? A cross-scale study.

The mechanisms of specific ion effects on the properties of amide macromolecules is essential to understanding the evolution of life. Because most biological macromolecules contain both complex hydrophilic and hydrophobic structures, it is challenging to accurately identify the contributions of molecular structure to macroscopic behaviors. Herein, we investigated the influence of specific ion effects on the mechanical behaviors of poly(N-isopropylacrylamide) and neutral polyacrylamide (i.e., PNIPAM and NPAM), through a cross-scale study that includes single-molecule force spectroscopy, molecular dynamics simulation and macro mechanical method. The results indicate that the molecular conformation can be markedly influenced by the hydrophilicity (or hydrophobicity) of both macromolecule chain and ions. An extended chain conformation can be obtained when the side groups and ions are relatively hydrophilic, which can also increase the elasticity of a macromolecule chain and film materials. The relatively hydrophobic components promote the collapse of macromolecule chains and reduce the molecular elasticity. It is believed that the hydrogen bonding intensity between a macromolecule chain and aquated ions controls the chain conformation and the elasticity of molecules and films. This study is not only helpful for understanding the self-assembly mechanism of organisms but also provides a way to associate the molecular properties with the macroscopic performance of materials.

Degradation pathways and product formation mechanisms of asphaltene in supercritical water

Asphaltene is the compound with the most complex structure and the most difficult degradation in oily sludge, which is the key to limit the efficiency of supercritical water oxidation treatment of oily sludge. In this paper, the supercritical water oxidation process of asphaltene was investigated in terms of free radical reaction, degradation pathway, and product generation mechanism using ReaxFF molecular dynamics simulation method. The results showed that increasing temperature, increasing O2, and increasing H2O have different effects on HO2·generation. Benzene rings undergo fusion and condensation through hydrogenation abstraction and oxygen addition reactions, subsequently breaking down into long-chain alkanes. Increasing O2 can effectively promote the ring-opening of nitrogen-containing heterocycles. -COOH is the most important intermediate fragment for CO and CO2 generation, and there is a reaction competition with -CHO3 and -CO3. When the number of oxygen molecules increases from 300 to 700, the reaction frequency of -CHO3 and -CO3 to generate CO and CO2 increases by 17.14 % and 12.77 %·H2O determines the production of H2 by controlling the number of H·radicals present. As the amount of H2O increases from 500 to 1500, the product ratio of H2 increases from 12.73 % to 21.31 %. Environmental implicationAsphaltene is the most structurally complex organic matter in oily sludge, and its presence makes it difficult for oily sludge to be completely degraded by conventional treatment methods such as pyrolysis and incineration. Polycyclic aromatic hydrocarbons (PAHs) represented by asphaltene increase the carcinogenicity and mutagenicity of oily sludge, and even irreversibly pollute soil and groundwater. Supercritical water oxidation, as an efficient organic waste treatment technology, can realize harmlessness in a green and efficient way. So the study on the mechanism of supercritical water oxidation of asphaltene is of great significance for environmental protection.

Rational Design of Non-Covalent Imprinted Polymers Based on the Combination of Molecular Dynamics Simulation and Quantum Mechanics Calculations.

Molecular imprinting is a promising approach for developing polymeric materials as artificial receptors. However, only a few types of molecularly imprinted polymers (MIPs) are commercially available, and most research on MIPS is still in the experimental phase. The significant limitation has been a challenge for screening imprinting systems, particularly for weak functional target molecules. Herein, a combined method of quantum mechanics (QM) computations and molecular dynamics (MD) simulations was employed to screen an appropriate 2,4-dichlorophenoxyacetic acid (2,4-D) imprinting system. QM calculations were performed using the Gaussian 09 software. MD simulations were conducted using the Gromacs2018.8 software suite. The QM computation results were consistent with those of the MD simulations. In the MD simulations, a realistic model of the 'actual' pre-polymerisation mixture was obtained by introducing numerous components in the simulations to thoroughly investigate all non-covalent interactions during imprinting. This study systematically examined MIP systems using computer simulations and established a theoretical prediction model for the affinity and selectivity of MIPs. The combined method of QM computations and MD simulations provides a robust foundation for the rational design of MIPs.

Reactant Discovery with an Ab Initio Nanoreactor: Exploration of Astrophysical N-Heterocycle Precursors and Formation Pathways.

The incorporation of nitrogen atoms into cyclic compounds is essential for terrestrial life; nitrogen-containing (N-)heterocycles make up DNA and RNA nucleobases, several amino acids, B vitamins, porphyrins, and other components of biomolecules. The discovery of these molecules on meteorites with non-terrestrial isotopic abundances supports the hypothesis of exogenous delivery of prebiotic material to early Earth; however, there has been no detection of these species in interstellar environments, indicating that there is a need for greater knowledge of their astrochemical formation and destruction pathways. Here, we present results of simulations of gas-phase pyrrole and pyridine formation from an ab initio nanoreactor, a first-principles molecular dynamics simulation method that accelerates reaction discovery by applying non-equilibrium forces that are agnostic to individual reaction coordinates. Using the nanoreactor in a retrosynthetic mode, starting with the N-heterocycle of interest and a radical leaving group, then considering the discovered reaction pathways in reverse, a rich landscape of N-heterocycle-forming reactivity can be found. Several of these reaction pathways, when mapped to their corresponding minimum energy paths, correspond to novel barrierless formation pathways for pyridine and pyrrole, starting from both detected and hypothesized astrochemical precursors. This study demonstrates how first-principles reaction discovery can build mechanistic knowledge in astrochemical environments as well as in early Earth models such as Titan's atmosphere where N-heterocycles have been tentatively detected.