@article{12758, abstract = {AlphaFold changed the field of structural biology by achieving three-dimensional (3D) structure prediction from protein sequence at experimental quality. The astounding success even led to claims that the protein folding problem is “solved”. However, protein folding problem is more than just structure prediction from sequence. Presently, it is unknown if the AlphaFold-triggered revolution could help to solve other problems related to protein folding. Here we assay the ability of AlphaFold to predict the impact of single mutations on protein stability (ΔΔG) and function. To study the question we extracted the pLDDT and metrics from AlphaFold predictions before and after single mutation in a protein and correlated the predicted change with the experimentally known ΔΔG values. Additionally, we correlated the same AlphaFold pLDDT metrics with the impact of a single mutation on structure using a large scale dataset of single mutations in GFP with the experimentally assayed levels of fluorescence. We found a very weak or no correlation between AlphaFold output metrics and change of protein stability or fluorescence. Our results imply that AlphaFold may not be immediately applied to other problems or applications in protein folding.}, author = {Pak, Marina A. and Markhieva, Karina A. and Novikova, Mariia S. and Petrov, Dmitry S. and Vorobyev, Ilya S. and Maksimova, Ekaterina and Kondrashov, Fyodor and Ivankov, Dmitry N.}, issn = {1932-6203}, journal = {PLoS ONE}, number = {3}, publisher = {Public Library of Science}, title = {{Using AlphaFold to predict the impact of single mutations on protein stability and function}}, doi = {10.1371/journal.pone.0282689}, volume = {18}, year = {2023}, } @article{12757, abstract = {My group and myself have studied respiratory complex I for almost 30 years, starting in 1994 when it was known as a L-shaped giant ‘black box' of bioenergetics. First breakthrough was the X-ray structure of the peripheral arm, followed by structures of the membrane arm and finally the entire complex from Thermus thermophilus. The developments in cryo-EM technology allowed us to solve the first complete structure of the twice larger, ∼1 MDa mammalian enzyme in 2016. However, the mechanism coupling, over large distances, the transfer of two electrons to pumping of four protons across the membrane remained an enigma. Recently we have solved high-resolution structures of mammalian and bacterial complex I under a range of redox conditions, including catalytic turnover. This allowed us to propose a robust and universal mechanism for complex I and related protein families. Redox reactions initially drive conformational changes around the quinone cavity and a long-distance transfer of substrate protons. These set up a stage for a series of electrostatically driven proton transfers along the membrane arm (‘domino effect'), eventually resulting in proton expulsion from the distal antiporter-like subunit. The mechanism radically differs from previous suggestions, however, it naturally explains all the unusual structural features of complex I. In this review I discuss the state of knowledge on complex I, including the current most controversial issues.}, author = {Sazanov, Leonid A}, issn = {1470-8728}, journal = {The Biochemical Journal}, number = {5}, pages = {319--333}, publisher = {Portland Press}, title = {{From the 'black box' to 'domino effect' mechanism: What have we learned from the structures of respiratory complex I}}, doi = {10.1042/BCJ20210285}, volume = {480}, year = {2023}, } @article{12787, abstract = {Populations evolve in spatially heterogeneous environments. While a certain trait might bring a fitness advantage in some patch of the environment, a different trait might be advantageous in another patch. Here, we study the Moran birth–death process with two types of individuals in a population stretched across two patches of size N, each patch favouring one of the two types. We show that the long-term fate of such populations crucially depends on the migration rate μ between the patches. To classify the possible fates, we use the distinction between polynomial (short) and exponential (long) timescales. We show that when μ is high then one of the two types fixates on the whole population after a number of steps that is only polynomial in N. By contrast, when μ is low then each type holds majority in the patch where it is favoured for a number of steps that is at least exponential in N. Moreover, we precisely identify the threshold migration rate μ⋆ that separates those two scenarios, thereby exactly delineating the situations that support long-term coexistence of the two types. We also discuss the case of various cycle graphs and we present computer simulations that perfectly match our analytical results.}, author = {Svoboda, Jakub and Tkadlec, Josef and Kaveh, Kamran and Chatterjee, Krishnendu}, issn = {1471-2946}, journal = {Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences}, number = {2271}, publisher = {The Royal Society}, title = {{Coexistence times in the Moran process with environmental heterogeneity}}, doi = {10.1098/rspa.2022.0685}, volume = {479}, year = {2023}, } @article{12788, abstract = {We show that the simplest of existing molecules—closed-shell diatomics not interacting with one another—host topological charges when driven by periodic far-off-resonant laser pulses. A periodically kicked molecular rotor can be mapped onto a “crystalline” lattice in angular momentum space. This allows us to define quasimomenta and the band structure in the Floquet representation, by analogy with the Bloch waves of solid-state physics. Applying laser pulses spaced by 1/3 of the molecular rotational period creates a lattice with three atoms per unit cell with staggered hopping. Within the synthetic dimension of the laser strength, we discover Dirac cones with topological charges. These Dirac cones, topologically protected by reflection and time-reversal symmetry, are reminiscent of (although not equivalent to) that seen in graphene. They—and the corresponding edge states—are broadly tunable by adjusting the laser strength and can be observed in present-day experiments by measuring molecular alignment and populations of rotational levels. This paves the way to study controllable topological physics in gas-phase experiments with small molecules as well as to classify dynamical molecular states by their topological invariants.}, author = {Karle, Volker and Ghazaryan, Areg and Lemeshko, Mikhail}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {10}, publisher = {American Physical Society}, title = {{Topological charges of periodically kicked molecules}}, doi = {10.1103/PhysRevLett.130.103202}, volume = {130}, year = {2023}, } @article{12790, abstract = {Motivated by the recent discoveries of superconductivity in bilayer and trilayer graphene, we theoretically investigate superconductivity and other interaction-driven phases in multilayer graphene stacks. To this end, we study the density of states of multilayer graphene with up to four layers at the single-particle band structure level in the presence of a transverse electric field. Among the considered structures, tetralayer graphene with rhombohedral (ABCA) stacking reaches the highest density of states. We study the phases that can arise in ABCA graphene by tuning the carrier density and transverse electric field. For a broad region of the tuning parameters, the presence of strong Coulomb repulsion leads to a spontaneous spin and valley symmetry breaking via Stoner transitions. Using a model that incorporates the spontaneous spin and valley polarization, we explore the Kohn-Luttinger mechanism for superconductivity driven by repulsive Coulomb interactions. We find that the strongest superconducting instability is in the p-wave channel, and occurs in proximity to the onset of Stoner transitions. Interestingly, we find a range of densities and transverse electric fields where superconductivity develops out of a strongly corrugated, singly connected Fermi surface in each valley, leading to a topologically nontrivial chiral p+ip superconducting state with an even number of copropagating chiral Majorana edge modes. Our work establishes ABCA-stacked tetralayer graphene as a promising platform for observing strongly correlated physics and topological superconductivity.}, author = {Ghazaryan, Areg and Holder, Tobias and Berg, Erez and Serbyn, Maksym}, issn = {2469-9969}, journal = {Physical Review B}, number = {10}, publisher = {American Physical Society}, title = {{Multilayer graphenes as a platform for interaction-driven physics and topological superconductivity}}, doi = {10.1103/PhysRevB.107.104502}, volume = {107}, year = {2023}, }