Foam films formed at the air-water interface do not have fixed adsorption sites where adsorbed surfactants can arrange themselves, resulting in the formation of thick adsorption layers. Current theories of equilibrium foam films fail to account for this feature and significantly underestimate the adsorption layer thickness. Here we show that this thickness has a significant effect on the disjoining pressure in foam films. If ignored, the theory predicts unphysical electrostatic potential profiles, which underestimate the disjoining pressure. We apply a previously developed adsorption model that incorporates a realistic thickness for the adsorption layer. This new model reproduces experimental measurements of the disjoining pressure of foam films very well over a wide surfactant concentration range without fitting parameters. Our work shows that a thick adsorption layer is less effectively screened by counterions, resulting in a higher electrostatic potential inside the film and therefore a higher disjoining pressure.Hairpin ribozyme catalyzes the reversible self-cleavage of phosphodiester bonds which plays prominent roles in key biological processes involving RNAs. Despite impressive advances on ribozymatic self-cleavage, critical aspects of its molecular reaction mechanism remain controversially debated. Here, we generate and analyze the multidimensional free energy landscape that underlies the reaction using extensive QM/MM metadynamics simulations to investigate in detail the full self-cleavage mechanism. This allows us to answer several pertinent yet controversial questions concerning activation of the 2′-OH group, the mechanistic role of water molecules present in the active site, and the full reaction pathway including the structures of transition states and intermediates. Importantly, we find that a sufficiently unrestricted reaction subspace must be mapped using accelerated sampling methods in order to compute the underlying free energy landscape. It is shown that lower-dimensional sampling where the bond formatiirpin ribozyme follows an AN + DN two-step associative pathway where the rate-determining step is the cleavage of the phosphodiester bond. These results provide a major advancement in our understanding of the unique catalytic mechanism of hairpin ribozyme which will fruitfully impact on the design of synthetic ribozymes.Membrane fusion of the viral and host cell membranes is the initial step of virus infection and is catalyzed by fusion peptides. Although the β-sheet structure of fusion peptides has been proposed to be the most important fusion-active conformation, it is still very challenging to experimentally identify different types of β-sheet structures at the cell membrane surface in situ and in real time. In this work, we demonstrate that the interface-sensitive amide II spectral signals of protein backbones, generated by the sum frequency generation vibrational spectroscopy, provide a sensitive probe for directly capturing the formation of oligomeric β-sheet structure of fusion peptides. Using human immunodeficiency virus (HIV) glycoprotein GP41 fusing peptide (FP23) as the model, we find that formation speed of oligomeric β-sheet structure depends on lipid unsaturation. The unsaturated lipid such as POPG can accelerate formation of oligomeric β-sheet structure of FP23. The β-sheet structure is more deeply inserted into the hydrophobic region of the POPG bilayer than the α-helical segment. Isradipine in vivo This work will pave the way for future researches on capturing intermediate structures during membrane fusion processes and revealing the fusion mechanism.Bis(phosphine) copper hydride complexes are uniquely able to catalyze direct dearomatization of unactivated pyridines with carbon nucleophiles, but the mechanistic basis for this result has been unclear. Here we show that, contrary to our initial hypotheses, the catalytic mechanism is monometallic and proceeds via dearomative rearrangement of the phenethylcopper nucleophile to a Cpara-metalated form prior to reaction at heterocycle C4. Our studies support an unexpected heterocycle-promoted pathway for this net 1,5-Cu-migration beginning with a doubly dearomative imidoyl-Cu-ene reaction. Kinetics, substituent effects, computational modeling, and spectroscopic studies support the involvement of this unusual process. In this pathway, the CuL2 fragment subsequently mediates a stepwise Cope rearrangement of the doubly dearomatized intermediate to the give the C4-functionalized 1,4-dihydropyridine, lowering a second barrier that would otherwise prohibit efficient asymmetric catalysis.The relationships between Kohn-Sham (KS) and generalized KS (GKS) density functional orbital energies and fundamental gaps or optical gaps raise many interesting questions including the physical meanings of KS and GKS orbital energies when computed with currently available approximate density functionals (ADFs). In this work, by examining three diverse databases with various ADFs, we examine such relations from the point of view of the exciton shift of quasiparticle theory. We start by calculating a large number of excitation energies by time-dependent density functional theory (TDDFT) with a large number of ADFs. To relate the exciton shift implicit in TDDFT to the exciton shift that is explicit in Green’s function theory, we define the exciton shift in TDDFT as the difference of the response shift and the quasiparticle shift. We found a strong correlation between the response shift and the amount of Hartree-Fock exchange included in the density functional, with the response shift varying between -1 and 5 eV. This range is an order of magnitude larger than the mean errors of the TDDFT excitation energies. This result suggests that, with currently available functionals, the KS or GKS orbital energies should be treated as intermediate mathematical variables in the calculation of excitation energies rather than as the energies of independent-particle reference states for quasiparticle theory.The neutral or A state of the green fluorescent protein (GFP) chromophore is a remarkable example of a photoacid naturally embedded in the protein environment and accounts for the large Stokes shift of GFP in response to near UV excitation. Its color tuning mechanism has been largely overlooked, as it is less preferred for imaging applications than the redder anionic or B state. Past studies, based on site-directed mutagenesis or solvatochromism of the isolated chromophore, have concluded that its color tuning range is much narrower than its anionic counterpart. However, as we performed extensive investigation on more GFP mutants, we found that the color of the neutral chromophore can be more sensitive to protein electrostatics than can the anionic counterpart. Electronic Stark spectroscopy reveals a fundamentally different electrostatic color tuning mechanism for the neutral state of the chromophore that demands a three-form model as compared to that of the anionic state, which requires only two forms ( J. Am.