Previous Molecular Dynamics Simulations Research Articles

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.

Ion permeation across the membrane: A comprehensive comparison analysis on passive permeations of differently charged ions

• The unassisted permeation of sulfide(-2 charge) in molecular details is explored. • The permeation of sulfide requires the coupling of cations, and causes little disturbance to the lipid bilayers. • The free energies of all ions and water, whether cation or anion, are highly correlated with the hydrophilic shell. • Membrane deformation, water wire or hydration can increase the energy barrier. Charge is very important for passive permeation of small molecules, but earlier research has led to different models of passive permeation of small molecules across lipid bilayer, which hardly achieved consistent and significant conclusions about the mechanism. Our previous molecular dynamics simulations on the transmembrane passive permeations of sodium, potassium, chloride and calcium ions had suggested molecular charge as one of the key factors in this process. Here we put more pieces into this puzzle by simulations on water (neutral) and sulfide (with two negative charges) molecules. The permeation profiles and free energies of all the ions mentioned above are comprehensively compared and analyzed, where the permeability coefficients calculated from this simulation are quite consistent with those from experiments. The permeation process of water is very simple, causing almost no perturbation to the lipid bilayers and fully conforming to the solubility-diffusion model, and the free energy barrier is very low. The permeation of sulfide needs to be accompanied by two sodium ions to offset its charges, and there is also little disturbance to the lipid bilayers. Based on the current study and comparison with previous ones, it is found that membrane deformation, water wire or hydration can increase the energy barrier. Specifically, the free energy of cation is more related to membrane deformation and water wire, while the free energy of anion is more related to hydration. More importantly, if the number of all oxygens including lipid oxygens and water oxygens within 0.5 nm of the ion is considered as an indicator of the “hydrophilic shell”, the free energies of all ions and water, whether cation or anion, are highly correlated with the hydrophilic shell. Hydrophilic shell is possible to be a valuable indicator that can be applied not only to ions, but also to molecules and even macromolecules due to its ubiquitous presence in the transmembrane permeation process of all substances.

A Functional Interaction Between Y674-R685 Region of the SARS-CoV-2 Spike Protein and the Human α7 Nicotinic Receptor.

The α7 nicotinic acetylcholine receptor (nAChR) is present in neuronal and non-neuronal cells and has anti-inflammatory actions. Molecular dynamics simulations suggested that α7 nAChR interacts with a region of the SARS-CoV-2 spike protein (S), and a potential contribution of nAChRs to COVID-19 pathophysiology has been proposed. We applied whole-cell and single-channel recordings to determine whether a peptide corresponding to the Y674-R685 region of the S protein can directly affect α7 nAChR function. The S fragment exerts a dual effect on α7. It activates α7 nAChRs in the presence of positive allosteric modulators, in line with our previous molecular dynamics simulations showing favourable binding of this accessible region of the S protein to the nAChR agonist binding site. The S fragment also exerts a negative modulation of α7, which is evidenced by a profound concentration-dependent decrease in the durations of openings and activation episodes of potentiated channels and in the amplitude of macroscopic responses elicited by ACh. Our study identifies a potential functional interaction between α7 nAChR and a region of the S protein, thus providing molecular foundations for further exploring the involvement of nAChRs in COVID-19 pathophysiology.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12035-022-02947-8.

Calculations of the Evolution of the Ca L23 Fine Structure in Amorphous Calcium Carbonate.

Amorphous calcium carbonate (ACC) has been found in many different organisms. Biogenic ACC is frequently a precursor in the formation of calcite and aragonite. The process of structural transformation is therefore of great interest in the study of crystallization pathways in biomineralization. Changes in the prepeak/main peak (L2'/L2) intensity ratio of the Ca L23-edge X-ray absorption spectroscopy (XAS) of Ca-rich particles in skeleton-building cells of sea urchin larva revealed that ACC precipitates through a continuum of states rather than through abrupt phase transitions involving two distinct phases as formerly believed. Using an atomic multiplet code, we show that only a tetragonal or "umbrella-like" distortion of the Ca coordination polyhedron can give rise to the observed continuum of states. We also show on the basis of the structures obtained from previous molecular dynamics simulations of hydrated nanoparticles that the Ca L23-edge is not sensitive to atomic arrangements in the early stages of the transformation process.

Phosphatidylserine and Phosphatidylethanolamine Asymmetry Have a Negligible Effect on the Global Structure, Dynamics, and Interactions of the KRAS Lipid Anchor.

The intrinsically disordered C-terminus of the prominent oncogenic protein KRAS-4B (KRAS) selectively interacts and clusters with phosphatidylserine (PS) lipids in the plasma membrane (PM). This 11-residue segment, called tK, contains a polybasic domain (PBD) of six contiguous lysine residues and a farnesylated cysteine. Previous molecular dynamics (MD) simulation studies of tK in phosphatidylcholine (PC)/PS bilayers have suggested that backbone conformational dynamics modulate tK-PS interactions. These simulations have been conducted in symmetric membranes whereas the PM is compositionally asymmetric, with the inner leaflet, where KRAS is localized, being enriched with PS and phosphatidylethanolamine (PE) lipids. To examine if bilayer asymmetry affects tK conformational dynamics and interaction with lipids, we conducted two 10 μs long MD simulations of tK bound to a PC/PS and a PC/PS/PE bilayer in which the PS and PE lipids are distributed in one leaflet. We found that, first, these compositional asymmetries caused differences in acyl chain dynamics between leaflets, but the equilibrium structural and dynamic properties of the two asymmetric bilayers are similar; second, in both systems tK is highly dynamic and samples at least two distinct conformational states; third, PS-tK hydrogen-bonding interactions vary with peptide backbone conformations, and lysine side chains in the PBD predominantly interact with the serine oxygens of PS. These results are in good agreement with previous observations of tK in symmetric membranes. The effects of POPS asymmetry or the presence of POPE on tK are limited to modulating the relative contribution of individual side chains to interactions with lipids and redistributing conformational substates. Additional observations include the larger flexibility of tK in the current simulations, which we attribute to the longer duration of the simulations and the use of the CHARMM36m force field, which more accurately models intrinsically disordered peptides such as tK.

Orientational disorder in sulfur hexafluoride: a neutron total scattering and reverse Monte Carlo study

The orientational disorder in crystalline sulfur hexafluoride, SF6, has been studied using a combination of neutron total scattering and the reverse Monte Carlo method. Analysis of the atomic configurations has shown the extent of the disorder through the evaluation of the S–F bond orientational distribution function, consistent with, but improving upon, the results of earlier neutron powder diffraction data. The correlations between orientations of neighbouring molecules have been studied through analysis of the distributions of F–F distances, showing that nearest-neighbour F–F close contacts are avoided, consistent with previous molecular dynamics simulation results. The results present a new case study of the application of neutron total scattering and the reverse Monte Carlo methods for the study of orientational disorder, where in this instance the disorder arises from orientational frustration rather than from a mismatch of molecular and site symmetries.

Influence of effective polarization on ion and water interactions within a biomimetic nanopore

Interactions between ions and water at hydrophobic interfaces within ion channels and nanopores are suggested to play a key role in the movement of ions across biological membranes. Previous molecular-dynamics simulations have shown that anion affinity for aqueous/hydrophobic interfaces can be markedly influenced by including polarization effects through an electronic continuum correction. Here, we designed a model biomimetic nanopore to imitate the polar pore openings and hydrophobic gating regions found in pentameric ligand-gated ion channels. Molecular-dynamics simulations were then performed using both a non-polarizable force field and the electronic-continuum-correction method to investigate the behavior of water, Na+, and Cl- ions confined within the hydrophobic region of the nanopore. Number-density distributions revealed preferential Cl- adsorption to the hydrophobic pore walls, with this interfacial layer largely devoid of Na+. Free-energy profiles for Na+ and Cl- permeating the pore also display an energy-barrier reduction associated with the localization of Cl- to this hydrophobic interface, and the hydration-number profiles reflect a corresponding reduction in the first hydration shell of Cl-. Crucially, these ion effects were only observed through inclusion of effective polarization, which therefore suggests that polarizability may be essential for an accurate description for the behavior of ions and water within hydrophobic nanoscale pores, especially those that conduct Cl-.

Allosteric networks regulate function in multi‐enzyme complexes

Networks of noncovalent amino acid interactions propagate allosteric signals throughout proteins. Tryptophan synthase (TS) is an allosterically controlled bienzyme in which the indole product of the alpha subunit (αTS) is transferred through a 25 Å hydrophobic tunnel to the active site of the beta subunit (βTS). Previous nuclear magnetic resonance and molecular dynamics simulations identified allosteric networks in αTS important for its function. Here, we show that these allosteric networks change across the catalytic cycle of αTS, such that chemical catalysis is associated with specific conformational dynamics and networks not observed in the substrate‐ and products‐bound states. Moreover, substitution of a distant, surface‐exposed network residue in αTS enhances tryptophan production, not by activating αTS function, but through dynamically controlling the opening of the indole channel and stimulating βTS activity. While stimulation is modest, the substitution also enhances cell growth in a tryptophan‐auxotrophic strain of Escherichia coli compared to complementation with wild‐type αTS, emphasizing the biological importance of the network. Network residues thus represent ideal targets to optimize mutagenesis strategies in protein engineering studies directed towards changing enzyme function and regulation, especially in multi‐enzyme complexes.

Simulating the diffusion of hydrogen in amorphous silicates: A ‘jumping’ migration process and its implications for solar wind implanted lunar volatiles

We use molecular dynamics (MD) simulations to better explain the movement of atomic hydrogen in amorphous silica and quantify the planetary science implications of these findings. Previous MD simulations had a large range of predicted values and did not agree well with experiment. Our simulations sample atomic motion for a longer duration and consider a wider range of temperatures than previous simulations. In contrast to constant atomic motion, the hydrogen atoms were shown to undergo random intermittent jumps from one oxygen atom to another, the number of which increase with temperature. Predicted diffusion coefficients had a better agreement to experimental values than previous MD simulations, suggesting the importance of longer simulation durations for better statistics. The low activation energy and jumps observed at lunar temperatures do not support the theory of diurnal variations in OH content for an undamaged amorphous silica surface. Instead, we conclude that energetic solar wind impacts can induce two competing atomic hydrogen motion processes in the exposed surface: A prompt effect that induces jumps in the temperature spike volume, but also a long-term effect of damage in the structure that traps atomic hydrogen. We then use SDTrimSP to quantify the damage created during exposure and MD to demonstrate the H retention and trapping near these defects. Damage was shown to be dependent on impact energy, with defects easily retaining implanted hydrogen. MD results like those presented herein on unweathered surfaces are therefore most relevant to magnetic anomalies. As a result, we demonstrate the importance of lunar volatile models to account for the damage state of the substrate when modelling hydrogen diffusion, retention, and subsequent OH/water production.

Effect of Cholesterol Molecules on Aβ1-42 Wild-Type and Mutants Trimers.

Alzheimer’s disease displays aggregates of the amyloid-beta (Aβ) peptide in the brain, and there is increasing evidence that cholesterol may contribute to the pathogenesis of the disease. Though many experimental and theoretical studies have focused on the interactions of Aβ oligomers with membrane models containing cholesterol, an understanding of the effect of free cholesterol on small Aβ42 oligomers is not fully established. To address this question, we report on replica exchange with a solute tempering simulation of an Aβ42 trimer with cholesterol and compare it with a previous replica exchange molecular dynamics simulation. We show that the binding hot spots of cholesterol are rather complex, involving hydrophobic residues L17–F20 and L30–M35 with a non-negligible contribution of loop residues D22–K28 and N-terminus residues. We also examine the effects of cholesterol on the trimers of the disease-causing A21G and disease-protective A2T mutations by molecular dynamics simulations. We show that these two mutations moderately impact cholesterol-binding modes. In our REST2 simulations, we find that cholesterol is rarely inserted into aggregates but rather attached as dimers and trimers at the surface of Aβ42 oligomers. We propose that cholesterol acts as a glue to speed up the formation of larger aggregates; this provides a mechanistic link between cholesterol and Alzheimer’s disease.

Taylor Impact Tests with Copper Cylinders: Experiments, Microstructural Analysis and 3D SPH Modeling with Dislocation Plasticity and MD-Informed Artificial Neural Network as Equation of State

Taylor impact tests involving the collision of a cylindrical sample with an anvil are widely used to study the dynamic properties of materials and to test numerical methods. We apply a combined experimental-numerical approach to study the dynamic plasticity of cold-rolled oxygen-free high thermal conductivity OFHC copper. In the experimental part, impact velocities up to 113.6 m/s provide a strain up to 0.3 and strain rates up to 1.7 × 104 s−1 at the edge of the sample. Microstructural analysis allows us to find out pore-like structures with a size of about 15–30 µm and significant refinement of the grain structure in the deformed parts of the sample. In terms of modeling, the dislocation plasticity model, which was previously tested for the problem of a shock wave upon impact of a plate, is implemented in the 3D case using the numerical scheme of smoothed particle hydrodynamics (SPH). The model includes an equation of state implemented in the form of an artificial neural network (ANN) and trained according to molecular dynamics (MD) simulations of uniform isothermal stretching/compression of representative volumes of copper. The dislocation friction coefficient is taken from previous MD simulations. These two efforts are aimed at building a fully MD-based material model. Comparison of the final shape of the projectile, the reduction of the sample length and increase in the diameter of the impacted edge of the sample confirm the applicability of the developed model and allow us to optimize the model parameters for the case of cold-rolled OFHC copper.

P-glycoprotein (ABCB1) - weak dipolar interactions provide the key to understanding allocrite recognition, binding, and transport.

P-glycoprotein (ABCB1) is the first discovered mammalian member of the large family of ATP binding cassette (ABC) transporters. It facilitates the movement of compounds (called allocrites) across membranes, using the energy of ATP binding and hydrolysis. Here, we review the thermodynamics of allocrite binding and the kinetics of ATP hydrolysis by ABCB1. In combination with our previous molecular dynamics simulations, these data lead to a new model for allocrite transport by ABCB1. In contrast to previous models, we take into account that the transporter was evolutionarily optimized to operate within a membrane, which dictates the nature of interactions. Hydrophobic interactions drive lipid-water partitioning of allocrites, the transport process's first step. Weak dipolar interactions (including hydrogen bonding, π-π stacking, and π-cation interactions) drive allocrite recognition, binding, and transport by ABCB1 within the membrane. Increasing the lateral membrane packing density reduces allocrite partitioning but enhances dipolar interactions between allocrites and ABCB1. Allocrite flopping (or reorientation of the polar part towards the extracellular aqueous phase) occurs after hydrolysis of one ATP molecule and opening of ABCB1 at the extracellular side. Rebinding of ATP re-closes the transporter at the extracellular side and expels the potentially remaining allocrite into the membrane. The high sensitivity of the steady-state ATP hydrolysis rate to the nature and number of dipolar interactions, as well as to the dielectric constant of the membrane, points to a flopping process, which occurs to a large extent at the membrane-transporter interface. The proposed unidirectional ABCB1 transport cycle, driven by weak dipolar interactions, is consistent with membrane biophysics.

Multiple conserved states characterize the twist landscape of the bacterial actin homolog MreB

Filament formation by cytoskeletal proteins is critical to their involvement in myriad cellular processes. The bacterial actin homolog MreB, which is essential for cell-shape determination in many rod-shaped bacteria, has served as a model system for studying the mechanics of cytoskeletal filaments. Previous molecular dynamics (MD) simulations revealed that the twist of MreB double protofilaments is dependent on the bound nucleotide, as well as binding to the membrane or the accessory protein RodZ, and MreB mutations that modulate twist also affect MreB spatial organization and cell shape. Here, we show that MreB double protofilaments can adopt multiple twist states during microsecond-scale MD simulations. A deep learning algorithm trained only on high- and low-twist states robustly identified all twist conformations across most perturbations of ATP-bound MreB, suggesting the existence of a conserved set of states whose occupancy is affected by each perturbation to MreB. Simulations replacing ATP with ADP indicated that twist states were generally stable after hydrolysis. These findings suggest a rich twist landscape that could provide the capacity to tune MreB activity and therefore its effects on cell shape.

Understanding gas absorption in multivalent ionic liquids via solute-solvent interaction analyses

Solute-solvent interactions are often evaluated to understand and explain gas solubilities. This information is regularly used to interpret gas solubility and separation within ionic liquids (ILs). Here, we use several different quantum chemical and previous molecular dynamics simulation results to show that strong solute–solvent interactions neither lead to high solubility nor to high selectivity, with respect to other solutes. Instead, the solute–solvent interaction strength with different isolated IL ions is affected by the electrostatic extremes. Also, the solute–solvent interaction with different IL molecules is strongly correlated to the molecular volumes or polarizabilities (within a series of same-anion based ILs).

Modeling lipid-protein interactions for coarse-grained lipid and Cα protein models.

Biological membranes that play major roles in diverse functions are composed of numerous lipids and proteins, making them an important target for coarse-grained (CG) molecular dynamics (MD) simulations. Recently, we have developed the CG implicit solvent lipid force field (iSoLF) that has a resolution compatible with the widely used Cα protein representation [D. Ugarte La Torre and S. Takada, J. Chem. Phys. 153, 205101 (2020)]. In this study, we extended it and developed a lipid-protein interaction model that allows the combination of the iSoLF and the Cα protein force field, AICG2+. The hydrophobic-hydrophilic interaction is modeled as a modified Lennard-Jones potential in which parameters were tuned partly to reproduce the experimental transfer free energy and partly based on the free energy profile normal to the membrane surface from previous all-atom MD simulations. Then, the obtained lipid-protein interaction is tested for the configuration and placement of transmembrane proteins, water-soluble proteins, and peripheral proteins, showing good agreement with prior knowledge. The interaction is generally applicable and is implemented in the publicly available software, CafeMol.

A particle‐continuum coupling method for multiscale simulations of viscoelastic–viscoplastic amorphous glassy polymers

AbstractIn this contribution, we present a partitioned‐domain method coupling a particle domain and a continuum domain for multiscale simulations of inelastic amorphous polymers under isothermal conditions. In the continuum domain, a viscoelastic–viscoplastic constitutive model calibrated from previous molecular dynamics (MD) simulations is employed to capture the inelastic properties of the polymer. Due to the material's rate‐dependence, a temporal coupling scheme is introduced. The influence of the time‐related parameters on the computational cost and accuracy is discussed. With appropriate parameters, multiscale simulations of glassy polystyrene under various loading conditions are implemented to showcase the method's capabilities to capture the mechanical behavior of polymers with different strain rates and with non‐affine deformations of the MD domain.

Simultaneous Analysis of Seismic Velocity and Electrical Conductivity in the Crust and the Uppermost Mantle: A Forward Model and Inversion Test Based on Grid Search

AbstractThis study presents a forward model to quantify the P‐wave velocity (VP), S‐wave velocity (VS), and electrical conductivity (σ) of the solid‐liquid mixtures for a given set of pressure, temperature, lithology, liquid phase (aqueous fluid or melt), liquid fraction, and geometrical parameters in relation to the aspect ratio and connectivity of the liquid phase. This is based on previous experimental and theoretical studies on seismic velocity and electrical conductivity of solid rocks and liquid phases. A total of 78 lithologies, an aqueous fluid with NaCl (∼0–10 wt.%), and mafic to felsic melt appropriate for the crust and the uppermost mantle conditions were described in terms of VP, VS, and σ, as per previous experimental measurements and molecular dynamics simulation. This forward model is provided as a Windows executable program, and generates synthetic VP, VS, and σ, referring to the seismic velocities and electrical conductivity observed in the northeast Japan arc. After generation of the synthetic VP, VS, and σ, the original lithology and liquid parameters (phase, fraction, aspect ratio, and connectivity) were searched by implementing the grid search algorithm to map the misfit over the broad parameter space. The mapping shows the presence of a global misfit minimum around the optimized solution and the possibility of resolving the lithology and the liquid phase parameters based on the observed VP, VS, and σ by using the forward model presented in this study.

Bridging the 12-6-4 Model and the Fluctuating Charge Model.

Metal ions play important roles in various biological systems. Molecular dynamics (MD) using classical force field has become a popular research tool to study biological systems at the atomic level. However, meaningful MD simulations require reliable models and parameters. Previously we showed that the 12-6 Lennard-Jones nonbonded model for ions could not reproduce the experimental hydration free energy (HFE) and ion-oxygen distance (IOD) values simultaneously when ion has a charge of +2 or higher. We discussed that this deficiency arises from the overlook of the ion-induced dipole interaction in the 12-6 model, and this term is proportional to 1/r 4 based on theory. Hence, we developed the 12-6-4 model and showed it could solve this deficiency in a physically meaningful way. However, our previous research also found that the 12-6-4 model overestimated the coordination numbers (CNs) for some highly charged metal ions. And we attributed this artifact to that the current 12-6-4 scheme lacks a correction for the interactions among the first solvation shell water molecules. In the present study, we considered the ion-included dipole interaction by using the 12-6 model with adjusting the atomic charges of the first solvation shell water molecules. This strategy not only considers the ion-induced dipole interaction between ion and the first solvation shell water molecules but also well accounts for the increased repulsion among these water molecules compared to the bulk water molecules. We showed this strategy could well reproduce the experimental HFE and IOD values for Mg2+, Zn2+, Al3+, Fe3+, and In3+ and solve the CN overestimation issue of the 12-6-4 model for Fe3+ and In3+. Moreover, our simulation results showed good agreement with previous ab initio MD simulations. In addition, we derived the physical relationship between the C 4 parameter and induced dipole moment, which agreed well with our simulation results. Finally, we discussed the implications of the present work for simulating metalloproteins. Due to the fluctuating charge model uses a similar concept to the 12-6 model with adjusting atomic charges, we believe the present study builds a bridge between the 12-6-4 model and the fluctuating charge model.

Substitution of a Surface-Exposed Residue Involved in an Allosteric Network Enhances Tryptophan Synthase Function in Cells.

Networks of noncovalent amino acid interactions propagate allosteric signals throughout proteins. Tryptophan synthase (TS) is an allosterically controlled bienzyme in which the indole product of the alpha subunit (αTS) is transferred through a 25 Å hydrophobic tunnel to the active site of the beta subunit (βTS). Previous nuclear magnetic resonance and molecular dynamics simulations identified allosteric networks in αTS important for its function. We show here that substitution of a distant, surface-exposed network residue in αTS enhances tryptophan production, not by activating αTS function, but through dynamically controlling the opening of the indole channel and stimulating βTS activity. While stimulation is modest, the substitution also enhances cell growth in a tryptophan-auxotrophic strain of Escherichia coli compared to complementation with wild-type αTS, emphasizing the biological importance of the network. Surface-exposed networks provide new opportunities in allosteric drug design and protein engineering, and hint at potential information conduits through which the functions of a metabolon or even larger proteome might be coordinated and regulated.

Understanding the Relation between Structural and Spectral Properties of Light-Harvesting Complex II.

Light-harvesting complex II (LHCII) is a pigment–protein complex present in higher plants and green algae. LHCII represents the main site of light absorption, and its role is to transfer the excitation energy toward the photosynthetic reaction centers, where primary energy conversion reactions take place. The optical properties of LHCII are known to depend on protein conformation. However, the relation between the structural and spectroscopic properties of the pigments is not fully understood yet. In this respect, previous classical molecular dynamics simulations of LHCII in a model membrane [Sci. Rep.2015, 5, 1–10] have shown that the configuration and excitonic coupling of a chlorophyll (Chl) dimer functioning as the main terminal emitter of the complex are particularly sensitive to conformational changes. Here, we use quantum chemistry calculations to investigate in greater detail the effect of pigment–pigment interactions on the excited-state landscape. While most previous studies have used a local picture in which electrons are localized on single pigments, here we achieve a more accurate description of the Chl dimer by adopting a supramolecular picture where time-dependent density functional theory is applied to the whole system at once. Our results show that specific dimer configurations characterized by shorter inter-pigment distances can result in a sizable intensity decrease (up to 36%) of the Chl absorption bands in the visible spectral region. Such a decrease can be predicted only when accounting for Chl–Chl charge-transfer excitations, which is possible using the above-mentioned supramolecular approach. The charge-transfer character of the excitations is quantified by two types of analyses: one focusing on the composition of the excitations and the other directly on the observable total absorption intensities.