Previous Molecular Dynamics Simulations Research Articles

Molecular Dynamics Study of Nanoribbon Formation by Encapsulating Cyclic Hydrocarbon Molecules inside Single-Walled Carbon Nanotube.

Carbon nanotubes filled with organic molecules can serve as chemical nanoreactors. Recent experimental results show that, by introducing cyclic hydrocarbon molecules inside carbon nanotubes, they can be transformed into nanoribbons or inner tubes, depending on the experimental conditions. In this paper, we present our results obtained as a continuation of our previous molecular dynamics simulation work. In our previous work, the initial geometry consisted of independent carbon atoms. Now, as an initial condition, we have placed different molecules inside a carbon nanotube (18,0): C5H5 (fragment of ferrocene), C5, C5+H2; C6H6 (benzene), C6, C6+H2; C20H12 (perylene); and C24H12 (coronene). The simulations were performed using the REBO-II potential of the LAMMPS software package, supplemented with a Lennard-Jones potential between the nanotube wall atoms and the inner atoms. The simulation proved difficult due to the slow dynamics of the H abstraction. However, with a slight modification of the parameterization, it was possible to model the formation of carbon nanoribbons inside the carbon nanotube.

Effects of -H and -OH Termination on Adhesion of Si-Si Contacts Examined Using Molecular Dynamics and Density Functional Theory.

The contact between nanoscale single-crystal silicon asperities and substrates terminated with -H and -OH functional groups is simulated using reactive molecular dynamics (MD). Consistent with previous MD simulations for self-mated surfaces with -H terminations only, adhesion is found to be low at full adsorbate coverages, be it self-mated coverages of mixtures of -H and -OH groups, or just -OH groups. As the coverage reduces, adhesion increases markedly, by factors of ∼5 and ∼6 for -H-terminated surfaces and -OH-terminated surfaces, respectively, and is due to the formation of covalent Si-Si bonds; for -OH-terminated surfaces, some interfacial Si-O-Si bonds are also formed. Thus, covalent linkages need to be broken upon separation of the tip and substrate. In contrast, replacing-Hgroups with -OH groups while maintaining complete coverage leads to negligible increases in adhesion. This indicates that increases in adhesion require unsaturated sites. Furthermore, plane-wave density functional theory (DFT) calculations were performed to investigate the energetics of two Si(111) surfaces fully terminated by either -H or -OH groups. Importantly for the adhesion results, both DFT and MD calculations predict the correct trends for the relative bond strengths: Si-O > Si-H > Si-Si. This work supports the contention that prior experimental work observing strong increases in adhesion after sliding Si-Si nanoasperities over each other is due to sliding-induced removal of passivating species on the Si surfaces.

Mesoscopic Model for Reversible Adsorption Stage of Albumin and Fibrinogen on TiO2 Surface.

The competitive behavior of proteins in the reversible adsorption stage plays a crucial role in determining the composition of the protein layer and the subsequent biological responses to the biomaterial. However, such competitive adsorption is a mesoscopic process at physiological protein concentration, and neither a macroscopic experiment nor microscopic MD (molecular dynamics) simulation is suitable to clarify it. Here, we proposed a mesoscopic DPD (dissipative particle dynamics) model to illustrate the competitive process of albumin and fibrinogen on TiO2 surface with its parameters deduced from our previous MD simulation, and proved the model well retained the diffusion and adsorption properties of proteins in the competitive adsorption on the plane surface. We then applied the model to the competitive adsorption on the surfaces with different nanostructures and observed that when the nanostructure size is much larger than that of protein, the increase in surface area is the main influencing factor; when the nanostructure size is close to that of protein, the coordination between the nanostructure and the size and shape of protein significantly affects the competitive adsorption process. The model has revealed many mechanical phenomena observed in previous experimental studies and has the potential to contribute to the development of high-performance biomaterials.

Machine Learning Models for Predicting Molecular Diffusion in Metal-Organic Frameworks Accounting for the Impact of Framework Flexibility.

Molecular diffusion in MOFs plays an important role in determining whether equilibrium can be reached in adsorption-based chemical separations and is a key driving force in membrane-based separations. Molecular dynamics (MD) simulations have shown that in some cases inclusion of framework flexibility in MOF changes predicted molecular diffusivities by orders of magnitude relative to more efficient MD simulations using rigid structures. Despite this, all previous efforts to predict molecular diffusion in MOFs in a high-throughput way have relied on MD data from rigid structures. We use a diverse data set of MD simulations in flexible and rigid MOFs to develop a classification model that reliably predicts whether framework flexibility has a strong impact on molecular diffusion in a given MOF/molecule pair. We then combine this approach with previous high-throughput MD simulations to develop a reliable model that efficiently predicts molecular diffusivities in cases in which framework flexibility can be neglected. The use of this approach is illustrated by making predictions of molecular diffusivities in ∼70,000 MOF/molecule pairs for molecules relevant to gas separations.

Renormalized charge and dielectric effects in colloidal interactions: a numerical solution of the nonlinear Poisson–Boltzmann equation for unknown boundary conditions

The Derjaguin–Landau–Verwey–Overbeek (DLVO) theory, introduced more than 70 years ago, is a hallmark of colloidal particle modeling. For highly charged particles in the dilute regime, it is often supplemented by Alexander’s prescription (Alexander et al. in J Chem Phys 80:5776, 1984) for using a renormalized charge. Here, we solve the problem of the interaction between two charged colloids at finite ionic strength, including dielectric mismatch effects, using an efficient numerical scheme to solve the nonlinear Poisson–Boltzmann (NPB) equation with unknown boundary conditions. Our results perfectly match the analytical predictions for the renormalized charge by Trizac and coworkers (Aubouy et al. in J Phys A 36:5835, 2003). Moreover, they allow us to reinterpret previous molecular dynamics (MD) simulation results by Kreer et al. (Phys Rev E 74:021401, 2006), rendering them now in agreement with the expected behavior. We furthermore find that the influence of polarization becomes important only when the Debye layers overlap significantly.Graphical

A hybrid off-lattice kinetic Monte Carlo/molecular dynamics method for amorphous thin film growth

The ability to understand and model the growth of amorphous thin films on solid surfaces is essential to a wide range of industrial applications, from the deposition of wear-resistant coatings to the production of solar cells. Here, a three-dimensional (3D) hybrid off-lattice kinetic Monte Carlo/molecular dynamics (kMC/MD) algorithm is developed to study the growth of thin amorphous films on solid substrates with atomistic resolution over timescales of tens of seconds. We use this method to study the growth of polyphosphate films from tricresyl phosphate (TCP) molecules on an iron substrate. Molecular adsorption/desorption, bond breaking/formation processes, and diffusion of iron ions through the film are simulated in the kMC stage and the film is relaxed during the MD stage. The kMC/MD method is approximately eleven orders of magnitude faster than equivalent reactive force field (ReaxFF) MD simulations. The simulated film growth rate and topology agree well with experimental results and the chemical structure of the film is consistent with previous molecular dynamics simulations of iron polyphosphates. The newly-developed hybrid kMC/MD methodology can be adapted to yield important insights into thin film growth for several other potential applications.

Detailed kinetic mechanism of polyoxymethylene dimethyl ether 3 (PODE3). Part I: Ab initio thermochemistry and kinetic predictions for key reactions

In recent years, polyoxymethylene dimethyl ether 3 (PODE3) has emerged as a promising fuel additive to mitigate soot emissions in diesel engines, garnering significant research attention. Several detailed kinetic mechanisms of PODE3 have been developed to investigate its reaction pathways and to simulate its combustion process. Typically, these mechanisms employ analogy methods based on rate constants derived primarily from PODE1 sub-mechanisms. However, in this study, we present, for the first time, high-level ab initio quantum chemical calculations directly on PODE3 itself. (1) The bond dissociation energies (BDEs) of all CH and CO bonds in dimethyl ether (DME) and PODEn (n = 1–5) were calculated using combined compound methods (CBS-APNO/G3/G4). (2) The obtained BDE results were then utilized to investigate the unimolecular decomposition reactions of PODE3, demonstrating good agreement with previous Molecular Dynamics simulation results. (3) The rate constants of hydrogen abstraction reactions of PODE3 by H˙,C˙H3,CH3O˙,O˙H,HO˙2,O2 were calculated with all possible pre-reaction or post-reaction complexes identified. The rate constants of the H-atom abstraction reactions were found to primarily depend on the energy barriers following the order: O˙H>CH3O˙>H˙>C˙H3>HO˙2>O2. However, the abstraction by H˙ can dominate as temperature increases. (4) The rate constants of β-scission and isomerization reactions of PODE3 radicals were also computed. The calculated β-scission reaction rates supported the suitability of the rate analogy for PODEn, employing the long-chain PODE3. The energy barriers of the isomerization reactions with long chain transition states were comparable to the energy barrier of the β-scission reactions and are much lower than that in the case of PODE1 radicals. (5) The thermochemistry properties of all involved species, including PODE4–5 and their radicals, were calculated with the combined compound methods (CBS-APNO/G3/G4) for further combustion modeling. Considering PODE3′s nature as a long-chain PODEn, the rate constants computed for PODE3 can serve as a solid foundation for developing detailed mechanisms for PODE4–5.

Fluid Properties Extraction in Confined Nanochannels with Molecular Dynamics and Symbolic Regression Methods.

In this paper, we propose an alternative road to calculate the transport coefficients of fluids and the slip length inside nano-conduits in a Poiseuille-like geometry. These are all computationally demanding properties that depend on dynamic, thermal, and geometrical characteristics of the implied fluid and the wall material. By introducing the genetic programming-based method of symbolic regression, we are able to derive interpretable data-based mathematical expressions based on previous molecular dynamics simulation data. Emphasis is placed on the physical interpretability of the symbolic expressions. The outcome is a set of mathematical equations, with reduced complexity and increased accuracy, that adhere to existing domain knowledge and can be exploited in fluid property interpolation and extrapolation, bypassing timely simulations when possible.

Antoine Equation Coefficients for Novichok Agents (A230, A232, and A234) via Molecular Dynamics Simulations

The flexible models of Novichok agents (A230, A232, and A234) from previous molecular dynamics simulations (MDSs) have been employed to create a parameter set for the Antoine equation of each of the three liquids. Furthermore, for the needs of this paper, new models of Novichok agents were created and studied via MDS due to the fact that the exact molecular structure of these compounds has been a matter of discussion in the last few years; however, recently, the literature favors a particular set of structures. Therefore, to cover our study holistically, both of the proposed molecular formulas were employed in the simulations and discussion. A range of ambient conditions was selected, and the data from the molecular dynamics simulations were employed to give the best possible fit in the selected vapor pressure range. When looking at the results for the two structures of A230, A232, and A234, we can see that, despite their differences, the A and B coefficients have the same magnitude in both cases (structures proposed by Ellison and Hoenig and structures proposed by Mirzayanov). Moving from the Ellison and Hoenig to Mirzayanov structures for substances A230 and A234 revealed a decrease (slight to major) in factors A and B of the Antoine equation. However, in the case of A232, where the Mirzayanov structure produces higher coefficients, this does not hold true. Overall, the Antoine equation of the studied agents will be an essential tool for understanding the behavior of these substances under different conditions.

Predicting evaporation/condensation mass fluxes using a chemical kinetics framework: Pseudo-chemical potential as the activation energy

A new model for evaporation/condensation is developed using a chemical kinetics framework. The unidirectional evaporation/condensation flux is calculated by the Arrhenius equation, in which the activation energy is assumed to be the pseudo-chemical potential (PCP) barrier and the pre-factor is determined by the collision frequency of liquid/vapor atoms. The value of the PCP barrier is obtained from the equilibrium molecular dynamics (MD) simulations of a liquid–vapor coexisting argon system using umbrella sampling. Simulation results show that the PCP barrier from vapor to liquid is zero, and that from liquid to vapor is the PCP difference between the two phases. The collision frequency can be derived from the Maxwell–Boltzmann velocity distribution, which is established in vapor and liquid phases. A density expression of the model is further derived by estimating the PCP barrier with the densities of the liquid and vapor. The condensation fluxes calculated from the original and density expressions are consistent with the results from the MD simulations of argon condensation. Moreover, the density expression of the new model has been validated by comparing it with results from previous MD simulations for verification purposes.

Engineering twin boundaries for enhancing strength and ductility of thermoelectric semiconductor PbTe

Twin boundary engineering is a potential strategy for achieving robust mechanical properties of materials. Our previous molecular dynamics simulations indicated that the nanotwin could significantly enhance the ductility of thermoelectric (TE) semiconductors PbTe due to coherent twin boundary (CTB) migration accompanied by the ‘catching bond’ at room temperature. To further improve the mechanical strength or ductility of PbTe, we investigated the role of the shear direction, the CTB orientation and the temperature on mechanical properties of nanotwinned PbTe. Under the shear stress along [11̅0] loading direction, the partial dislocations with a/6 [12̅1] and a/6 [21̅1̅] Burgers vectors are preferentially activated on (111) twin plane with higher yield strength and ultimate shear strength than that of the (111)[112̅] slip system. The nanotwinned PbTe with CTB orientation ranging from 125° to 161° has both higher fracture strain and larger ultimate shear strength than 0° CTB orientation. This is attributed to the motion of the twinning partial dislocation significantly enhancing the ductility while the blocking of dislocations by CTBs further improving the shear strength and deformability of PbTe. Moreover, the low temperature (below 100 K) energetically enables the partial dislocation to nucleate and glide on the strong Te-CTB plane, which induces successive CTB migration along Pb- and Te-CTB planes, resulting in enhanced ductility of nanotwinned PbTe.

Confining CO2 inside sI clathrate‐hydrates: The impact of the CO2–water interaction on quantized dynamics

We report new results on the translational-rotational (T-R) states of the CO2 molecule inside the sI clathrate-hydrate cages. We adopted the multiconfiguration time-dependent Hartree methodology to solve the nuclear molecular Hamiltonian, and to address issues on the T-R couplings. Motivated by experimental X-ray observations on the CO2 orientation in the D and T sI cages, we aim to evaluate the effect of the CO2 -water interaction on quantum dynamics. Thus, we first compared semiempirical and ab initio-based pair interaction model potentials against first-principles DFT-D calculations for ascertaining the importance of nonadditive many-body effects on such guest-host interactions. Our results reveal that the rotational and translational excited states quantum dynamics is remarkably different, with the pattern and density of states clearly affected by the underlying potential model. By analyzing the corresponding the probability density distributions of the calculated T-R eigenstates on both semiempirical and ab initio pair CO2 -water nanocage potentials, we have extracted information on the altered CO2 guest local structure, and we discussed it in connection with experimental data on the orientation of the CO2 molecule in the D and T sI clathrate cages available from neutron diffraction and solid-state NMR studies, as well as in comparison with previous molecular dynamics simulations. Our calculations provide a very sensitive test of the potential quality by predicting the low-lying T-R states and corresponding transitions for the encapsulated CO2 molecule. As such spectroscopic observables have not been measured so far, our results could trigger further detailed experimental and theoretical investigations leading to a quantitative description of the present guest-host interactions.

Torque generation mechanism in Fo motor of ATP synthase elucidated by free-energy and Coulomb-energy landscapes along the c-ring rotation

Fo portion of ATP synthase is a proton-motive rotary motor. The Coulombic attraction between the conserved acidic residues in the c-ring and the arginine in the a-subunit (aR) was early proposed to drive the c-ring rotation relative to the a-subunit, and has been actually observed in our previous molecular dynamics simulation with full atomistic description of Fo embedded in the membrane. In this study, to quantify the driving force, we conducted the umbrella sampling (US) and obtained the free-energy landscape for the c-ring rotation. We first show that the free-energy gradient toward the ATP-synthesis direction appears in the deprotonated state of cE. Using the sampled snapshots that cover a wide range of the rotational angle, we further analyzed the rotational-angle dependence of the hydration and the protonation states and obtained the Coulomb-energy landscapes with a focus on the cE-aR interaction. The results indicate that both the Coulombic solvation energy of cE and the interaction energy between cE and aR contribute to the torque generation for the c-ring rotation.

Curious case of a leaky mitochondria.

The mitochondrial permeability transition pore (mPTP) leads to cell death upon its activation. The past several decades have seen many studies regarding the modulation of the mPTP, but little is known about the structure. There has been a growing body of evidence that the ATP synthase c-subunit houses the mPTP leak channel. Experimental evidence has shown that ATP Synthase forms voltage-gated and Ca2+-activated channels, consistent to what is known about mPTP activation. Previous experimental and molecular dynamics simulation studies demonstrate that the ATP synthase c-subunit is occupied by lipid and/or detergent molecules, claiming that a leak channel cannot be formed and that ATP synthase does not play a role in mPTP formation. These studies have sparked much controversy regarding the structural identity of the mPTP leak channel. In this work, we investigated whether the ATP synthase c-subunit forms a leak channel upon introducing voltage. We performed molecular dynamics simulations on the ATP synthase c-subunit under an electric field, ranging from −180 mV to +180 mV. Our results show significant expansion of the c-subunit, and lipids exiting as water leaks into the pore. Additionally, we identified a dipole on the c-subunit monomer that aids in voltage-sensing. We also applied voltage to a c-subunit high and low-conductance mutants, where we observe similar results, except for decreased water leakage in the low-conductance mutant. Initially, we observed a bottleneck at a key glutamic acid residue that is responsible for proton transport in the c-subunit. To overcome this bottleneck, we introduced a series of deprotonations on these glutamic acid residues to promote water accessibility, resulting in a full leak channel formation. With our results, we seek to answer a long-standing question about the gating mechanism of ATP synthase c-subunit leak channel and the structural identity of the mPTP.

Energy deposition and formation of nanostructures in the interaction of highly charged xenon ions with gold nanolayers

The effect of the deposition of kinetic energy and neutralization energy of slow highly charged xenon ions on the process of the nanostructures creation at the surface of gold nanolayers is investigated. The nanolayers of thickness of 100 nm were prepared by e-beam evaporation of gold on crystalline silicon Si(100) substrate. The samples were irradiated at the Kielce EBIS facility of the Jan Kochanowski University (Kielce, Poland), under high vacuum conditions. The irradiations were performed for constant kinetic energy 280 keV and different ions charge states (Xeq+, q = 25, 30, 35, 36 and 40) and for constant charge state Xe35+ and different kinetic energies: 280 keV, 360 keV, 420 keV and 480 keV. The fluence of the ions was on the level of 1010 ions/cm2. Before and after irradiation the nanolayer surfaces were investigated using the atomic force microscope.As the result, well pronounced modifications of the nanolayer surfaces in the form of craters have been observed. A systematic analysis of the crater sizes (diameter on the surface and depth) allowed us to determine the influence of the deposited kinetic and the neutralization energy on the size of the obtained nanostructures. The results are theoretically interpreted within the micro-staircase model based on the quantum two-state vector model of the ionic Rydberg states population. The charge dependent ion–atom interaction potential inside the solid is used for the calculation of the nuclear stopping power. According to the model the formation of the nanostructures is governed by the processes of the ionic neutralization in front of the surface and the kinetic energy loss inside the solid. The interplay of these two types of processes in the surface structure creation is described by the critical velocity. Using the proposed theoretical model, the neutralization energy, deposited kinetic energy and critical velocities were calculated and compared qualitatively with the experimental results. The results are consistent (after normalization) with previous experimental data and molecular dynamics simulations for single ionized Xe and crystalline gold surface.

Molecular Dynamics Simulation of the Thermal Diffusion Effect in n-Alkane Binary Mixtures.

In oil and gas reservoirs, the thermal diffusion effect leads to compositional variations of hydrocarbon fluids in both horizontal and vertical directions. Compared with experimental methods, molecular dynamics (MD) simulations can cover a broader range of pressures and temperatures for the investigation of the thermal diffusion effect. However, previous MD simulations of the thermal diffusion effect for n-alkane binary mixtures have been limited to only nC5-nC10, nC6-nC10, and nC6-nC12 mixtures. In this work, for the first time, we perform a series of MD simulations on n-alkane binary mixtures, C1-C3, C1-nC4, nC7-nC12, nC7-nC16, and nC10-nCi (i = 5, 7, 8, 12, 14, 16), with different mole fractions and temperature and pressure conditions. The boundary-driven nonequilibrium molecular dynamics (BD-NEMD) with the enhanced heat exchange (eHEX) algorithm is used to generate the temperature gradient and measure the thermal diffusion effect. Additionally, a workflow for molecular simulations of thermal diffusion of n-alkane binary mixtures is proposed to ensure their repeatability and reliability. The errors for our MD simulation results are generally less than 10% compared with experimental data. Our results show that in the binary mixture, the heavy component tends to move to the cold region, while the lighter component tends to aggregate near the hot region, which is consistent with experimental observations.

'Targeting' the search: An upgraded structural and functional repository of antimicrobial peptides for biofilm studies (B-AMP v2.0) with a focus on biofilm protein targets.

Bacterial biofilms, often as multispecies communities, are recalcitrant to conventional antibiotics, making the treatment of biofilm infections a challenge. There is a push towards developing novel anti-biofilm approaches, such as antimicrobial peptides (AMPs), with activity against specific biofilm targets. In previous work, we developed Biofilm-AMP, a structural and functional repository of AMPs for biofilm studies (B-AMP v1.0) with more than 5000 structural models of AMPs and a vast library of AMP annotations to existing biofilm literature. In this study, we present an upgraded version of B-AMP, with a focus on existing and novel bacterial biofilm targets. B-AMP v2.0 hosts a curated collection of 2502 biofilm protein targets across 473 bacterial species, with structural protein models and functional annotations from PDB, UniProt, and PubMed databases. The biofilm targets can be searched for using the name of the source organism, and function and type of protein, and results include designated Target IDs (unique to B-AMP v2.0), UniProt IDs, 3D predicted protein structures, PDBQT files, pre-defined protein functions, and relevant scientific literature. To present an example of the combined applicability of both, the AMP and biofilm target libraries in the repository, we present two case studies. In the first case study, we expand an in silico pipeline to evaluate AMPs against a single biofilm target in the multidrug resistant, bacterial pathogen Corynebacterium striatum, using 3D protein-peptide docking models from previous work and Molecular Dynamics simulations (~1.2µs). In the second case study, we build an in silico pipeline to identify candidate AMPs (using AMPs with both anti-Gram positive and anti-Gram negative activity) against two biofilm targets with a common functional annotation in Pseudomonas aeruginosa and Staphylococcus aureus, widely-encountered bacterial co-pathogens. With its enhanced structural and functional capabilities, B-AMP v2.0 serves as a comprehensive resource for AMP investigations related to biofilm studies. B-AMP v2.0 is freely available at https://b-amp.karishmakaushiklab.com and will be regularly updated with structural models of AMPs and biofilm targets, as well as 3D protein-peptide interaction models for key biofilm-forming pathogens.

Helicene Structure between DNA and Cyanuric Acid: The Role of Noncovalent Interactions.

The self-assembly between DNA and small organic molecules can expand the structural space of and introduce novel functionalities to DNA nanomaterials. In particular, it was demonstrated that poly(adenosine) DNA self-assembles with cyanuric acid (CA) to form a triplex helical structure. Previous molecular dynamics simulations showed that the DNA-CA assemblies adopt a novel noncovalent helicene structure that has a continuous helical hydrogen bond network. This article explores why the assemblies adopt the helicene geometry instead of an alternative planar hexameric rosette geometry. Analysis of the hydrogen bonding and stacking interaction energies indicates that constraining the system to the hexameric rosette geometry strains the hydrogen bonds without significantly improving the interaction energy. Molecular dynamics simulations for the assemblies between adenosine nucleosides and CA confirm that the formation of helicene structure is primarily driven by base-pair interactions and not because of the DNA backbone.

Revisiting the melting curves of vanadium and niobium metals under pressure

The Lindemann criterion is adjusted to revisit melting curves of vanadium and niobium metals under pressure thanks to the statistical moment method (SMM) in statistical mechanics. The equation-of-state and atomic mean-square displacement in SMM approach are applied to implement numerical calculations for vanadium and niobium metals up to 250 GPa and 150 GPa, respectively. The obtained theoretical melting curves are compared with results of previous experiments and molecular dynamics (MD) simulations where possible to check the theory. We expose that our theoretical melting line of vanadium is overall in good agreement with previous results determined by in situ X-ray diffraction (XRD) and diffuse scattering signals using synchrotron XRD together with shock experiments up to pressure 250GPa. For niobium, our melting curve follows very well with those of recent experimental XRD data as well as ab initio Z method up to 124 GPa. However, we also observe the difference of classical MD simulation results from SMM calculations at pressure below 2.5 GPa. This research enriches the high-pressure melting point database as well as provides a relatively simple approach with low computational cost to estimate high-pressure melting points of materials.

Lipid Modulation of a Class B GPCR: Elucidating the Modulatory Role of PI(4,5)P2 Lipids.

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) lipids have been shown to stabilize an active conformation of class A G-protein coupled receptors (GPCRs) through a conserved binding site, not present in class B GPCRs. For class B GPCRs, previous molecular dynamics (MD) simulation studies have shown PI(4,5)P2 interacting with the Glucagon receptor (GCGR), which constitutes an important target for diabetes and obesity therapeutics. In this work, we applied MD simulations supported by native mass spectrometry (nMS) to study lipid interactions with GCGR. We demonstrate how tail composition plays a role in modulating the binding of PI(4,5)P2 lipids to GCGR. Specifically, we find the PI(4,5)P2 lipids to have a higher affinity toward the inactive conformation of GCGR. Interestingly, we find that in contrast to class A GPCRs, PI(4,5)P2 appear to stabilize the inactive conformation of GCGR through a binding site conserved across class B GPCRs but absent in class A GPCRs. This suggests differences in the regulatory function of PI(4,5)P2 between class A and class B GPCRs.