Interaction of β-Sheet Folds with a Gold Surface

The adsorption of proteins on inorganic surfaces is of fundamental biological importance. Further, biomedical and nanotechnological applications increasingly use interfaces between inorganic material and polypeptides. Yet, the underlying adsorption mechanism of polypeptides on surfaces is not well understood and experimentally difficult to analyze. Therefore, we investigate here the interactions of polypeptides with a gold(111) surface using computational molecular dynamics (MD) simulations with a polarizable gold model in explicit water. Our focus in this paper is the investigation of the interaction of polypeptides with β-sheet folds. First, we concentrate on a β-sheet forming model peptide. Second, we investigate the interactions of two domains with high β-sheet content of the biologically important extracellular matrix protein fibronectin (FN). We find that adsorption occurs in a stepwise mechanism both for the model peptide and the protein. The positively charged amino acid Arg facilitates the initial contact formation between protein and gold surface. Our results suggest that an effective gold-binding surface patch is overall uncharged, but contains Arg for contact initiation. The polypeptides do not unfold on the gold surface within the simulation time. However, for the two FN domains, the relative domain-domain orientation changes. The observation of a very fast and strong adsorption indicates that in a biological matrix, no bare gold surfaces will be present. Hence, the bioactivity of gold surfaces (like bare gold nanoparticles) will critically depend on the history of particle administration and the proteins present during initial contact between gold and biological material. Further, gold particles may act as seeds for protein aggregation. Structural re-organization and protein aggregation are potentially of immunological importance

Sample-dependent Dirac-point gap in MnBi2Te4 and its response to applied surface charge: A combined photoemission and ab initio study

Recently discovered intrinsic antiferromagnetic topological insulator MnBi2Te4 presents an exciting platform for realization of the quantum anomalous Hall effect and a number of related phenomena at elevated temperatures. An important characteristic making this material attractive for applications is its predicted large magnetic gap at the Dirac point (DP). However, while the early experimental measurements reported on large DP gaps, a number of recent studies claimed to observe a gapless dispersion of the MnBi2Te4 Dirac cone. Here, using micro(μ)-laser angle-resolved photoemission spectroscopy, we study the electronic structure of 15 different MnBi2Te4 samples, grown by two different chemists groups. Based on the careful energy distribution curves analysis, the DP gaps between 15 and 65 meV are observed, as measured below the Néel temperature at about 10–16 K. At that, roughly half of the studied samples show the DP gap of about 30 meV, while for a quarter of the samples the gaps are in the 50 to 60 meV range. Summarizing the results of both our and other groups, in the currently available MnBi2Te4 samples the DP gap can acquire an arbitrary value between a few and several tens of meV. Furthermore, based on the density functional theory, we discuss a possible factor that might contribute to the reduction of the DP gap size, which is the excess surface charge that can appear due to various defects in surface region. We demonstrate that the DP gap is influenced by the applied surface charge and even can be closed, which can be taken advantage of to tune the MnBi2Te4 DP gap size.The authors acknowledge support by the Saint Petersburg State University Grant No. ID 73028629, Russian Science Foundation Grant No. 18-12-00062 in part of the photoemission measurements and total analysis of the results, Grant No. 18-12-00169-p in part of the electronic band structure calculations and Grant No. 20-42-08002 in part of analysis of magnetic properties and Science Development Foundation under the President of the Republic of Azerbaijan Grant No. EI F-BGM-4-RFTF1/2017-21/04/1-M-02. M.M.O. acknowledges the support by Spanish Ministerio de Ciencia e Innovación (Grant No. PID2019-103910GB-I00). K.K. and O.E.T. acknowledge the support from state assignment of IGM SB RAS and ISP SB RAS.Peer reviewe

Kinetics for Drug Discovery: an industry-driven effort to target drug residence time

A considerable number of approved drugs show non-equilibrium binding characteristics, emphasizing the potential role of drug residence times for in vivo efficacy. Therefore, a detailed understanding of the kinetics of association and dissociation of a target-ligand complex might provide crucial insight into the molecular mechanism-of-action of a compound. This deeper understanding will help to improve decision making in drug discovery, thus leading to a better selection of interesting compounds to be profiled further. In this review, we highlight the contributions of the Kinetics for Drug Discovery (K4DD) Consortium, which targets major open questions related to binding kinetics in an industry-driven public-private partnership.PharmacologyMedicinal Chemistr

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Optical properties of β-BBO and potential for THz applications

The anisotropy of optical properties of high quality beta barium borate crystal (β-BaB2O4, β-BBO) was studied in the main transparency window by using classic spectroscopic methods and in the range of 0.2 – 2 THz by using THz time-domain spectroscopy. β-BBO crystals were grown by the top-seeded solution technique in a highly resistive furnace with a heat field of 3-fold axis symmetry. At room temperature (RT), absorption coefficient in the maximal transparency window in grown crystals did not exceed 0.05 cm-1. Strong absorption anisotropy was observed in 3 – 5 μm and the THz range. At 1 THz absorption coefficients for e and o wave were, respectively, 7 cm-1 and 21 cm-1 at RT; 2 cm-1 and 10 cm-1 at 81 K. At the most attractive for out-of-door applications range < 0.4 THz the absorption coefficient is found to be very low: below 0.2 cm-1 at RT and 1 cm-1 at 81 K. Refractive indices dispersions measured by THz-TDS were approximated in the form of Sellmeier equations. Birefringence is found quite large for phase matched difference frequency generation (DFG) or down-conversion into the THz range (THz-DFG) under near IR pump at RT and 81 K. Type II (oe-o and eo-o), and type I (ee-e) three wave interactions can be realized at RT. THz-DFG of Nd:YAG laser and KTP OPO can be realized by type II (oe-o) three-wave interaction. For selected spectral ranges of femtosecond Ti:Sapphire laser efficient phase matched and group velocity matched optical rectification can be realized by another two types of three wave interactions. Accounting other well-known attractive physical properties of β-BBO crystal, wide application in THz technique can be forecasted