MEPSA: Minimum energy pathway analysis for energy landscapes

From conformational studies to atomistic descriptions of enzymatic reactions, potential and free energy landscapes can be used to describe biomolecular systems in detail. However, extracting the relevant data of complex 3D energy surfaces can sometimes be laborious. In this article, we present MEPSA (Minimum Energy Path Surface Analysis), a cross-platform user friendly tool for the analysis of energy landscapes from a transition state theory perspective. Some of its most relevant features are: identification of all the barriers and minima of the landscape at once, description of maxima edge profiles, detection of the lowest energy path connecting two minima and generation of transition state theory diagrams along these paths. In addition to a built-in plotting system, MEPSA can save most of the generated data into easily parseable text files, allowing more versatile uses of MEPSA's output such as the generation of molecular dynamics restraints from a calculated path.Grant IPT2011-0964-900000 (Government of Spain).Peer Reviewe

DFT molecular dynamics and free energy analysis of a charge density wave surface system

This Accepted Manuscript will be available for reuse under a CC BY-NC-ND licence after 24 months of embargo periodThe K/Si(111):B 3×3 surface, with one K atom per 3×3 unit cell, is considered a prototypical case of a surface Mott phase at room temperature. Our Density Functional Theory (DFT) Molecular Dynamics (MD) and free energy calculations show, however, a 23×3 Charge Density Wave (CDW) ground state. Our analysis shows that at room temperature the K atoms easily diffuse along the lines of a honeycomb network on the surface and that the 3×3 phase appears as the result of the dynamical fluctuations between degenerate CDW states. DFT-MD free energy calculations also show a 23×3↔3×3 transition temperature below 90 K. The competing electron-electron and electron-phonon interactions at low temperature are also analyzed; using DFT calculations, we find that the electron-phonon negative-U * is larger than the electron-electron Hubbard U, indicating that the CDW survives at very low temperatureThis work was supported by grant nos. MAT2014-59966-R and MAT2017-88258-R from the Ministerio de Economía, Industria y Competitividad (Spain

Two-step ATP-driven opening of cohesin head.

The cohesin ring is a protein complex composed of four core subunits: Smc1A, Smc3, Rad21 and Stag1/2. It is involved in chromosome segregation, DNA repair, chromatin organization and transcription regulation. Opening of the ring occurs at the “head” structure, formed of the ATPase domains of Smc1A and Smc3 and Rad21. We investigate the mechanisms of the cohesin ring opening using techniques of free molecular dynamics (MD), steered MD and quantum mechanics/molecular mechanics MD (QM/MM MD). The study allows the thorough analysis of the opening events at the atomic scale: i) ATP hydrolysis at the Smc1A site, evaluating the role of the carboxy-terminal domain of Rad21 in the process; ii) the activation of the Smc3 site potentially mediated by the movement of specific amino acids; and iii) opening of the head domains after the two ATP hydrolysis events. Our study suggests that the cohesin ring opening is triggered by a sequential activation of the ATP sites in which ATP hydrolysis at the Smc1A site induces ATPase activity at the Smc3 site. Our analysis also provides an explanation for the effect of pathogenic variants related to cohesinopathies and cancer.post-print4709 K

Structural Expansion of Cyclohepta[def]fluorene towards Azulene-Embedded Non-Benzenoid Nanographenes

Non-benzenoid non-alternant nanographenes (NGs) have attracted increasing attention on account of their distinct electronic and structural features in comparison to their isomeric benzenoid counterparts. In this work, we present a series of unprecedented azulene-embedded NGs on Au(111) during the attempted synthesis of cyclohepta[def]fluorene-based high-spin non-Kekulé structure. Comprehensive scanning tunneling microscopy (STM) and non-contact atomic force microscopy (nc-AFM) evidence the structures and conformations of these unexpected products. The dynamics of the precursor bearing 9-(2,6-dimethylphenyl)anthracene and dihydro-dibenzo-cyclohepta[def]fluorene units and its reaction products on the surface are analyzed by density functional theory (DFT) and molecular dynamics (MD) simulations. Our study sheds light on the fundamental understanding of precursor design for the fabrication of π-extended non-benzenoid NGs on a metal surfaceThis research was financially supported by the EU Graphene Flagship (Graphene Core 3, 881603), ERC Consolidator Grant (T2DCP, 819698), H2020-MSCA-ITN (ULTIMATE, No. 813036), the Center for Advancing Electronics Dresden (cfaed), H2020- EU.1.2.2. – FET Proactive Grant (LIGHT-CAP, 101017821) and the DFG-SNSF Joint Switzerland-German Research Project (EnhanTopo, No. 429265950). This project has received funding from Ministerio de Ciencia, Innovacion y Universidades (PID2019-108532GB-I00). IMDEA Nanociencia is appreciative of support from the “(MAD2D-CM)” project funded by Comunidad de Madrid, by the Recovery, Transformation and Resilience Plan, and by NextGenerationEU from the European Union; and from the “Severo Ochoa” Programme for Centers of Excellence in R&D (MINECO, grants SEV-2016-0686 and CEX2020-001039-S). The authors gratefully acknowledge the GWK support for funding this project by providing computing time through the Center for Information Services and HPC (ZIH) at TU Dresden and the Computational resources e-INFRA CZ project (ID:90254), supported by the Ministry of Education, Youth and Sports of the Czech Republic. Open Access funding enabled and organized by Projekt DEA

Significance of nuclear quantum effects in hydrogen bonded molecular chains

In hydrogen bonded systems, nuclear quantum effects such as zero-point motion and tunneling can significantly affect their material properties through underlying physical and chemical processes. Presently, direct observation of the influence of nuclear quantum effects on the strength of hydrogen bonds with resulting structural and electronic implications remains elusive, leaving opportunities for deeper understanding to harness their fascinating properties. We studied hydrogen-bonded one-dimensional quinonediimine molecular networks which may adopt two isomeric electronic configurations via proton transfer. Herein, we demonstrate that concerted proton transfer promotes a delocalization of {\pi}-electrons along the molecular chain, which enhances the cohesive energy between molecular units, increasing the mechanical stability of the chain and giving rise to new electronic in-gap states localized at the ends. These findings demonstrate the identification of a new class of isomeric hydrogen bonded molecular systems where nuclear quantum effects play a dominant role in establishing their chemical and physical properties. We anticipate that this work will open new research directions towards the control of mechanical and electronic properties of low-dimensional molecular materials via concerted proton tunneling

Molecular sensitised probe for amino acid recognition within peptide sequences

The combination of low-temperature scanning tunnelling microscopy with a mass-selective electro-spray ion-beam deposition established the investigation of large biomolecules at nanometer and sub-nanometer scale. Due to complex architecture and conformational freedom, however, the chemical identification of building blocks of these biopolymers often relies on the presence of markers, extensive simulations, or is not possible at all. Here, we present a molecular probe-sensitisation approach addressing the identification of a specific amino acid within different peptides. A selective intermolecular interaction between the sensitiser attached at the tip-apex and the target amino acid on the surface induces an enhanced tunnelling conductance of one specific spectral feature, which can be mapped in spectroscopic imaging. Density functional theory calculations suggest a mechanism that relies on conformational changes of the sensitiser that are accompanied by local charge redistributions in the tunnelling junction, which, in turn, lower the tunnelling barrier at that specific part of the peptide

Attomolar detection of hepatitis C virus core protein powered by molecular antenna-like effect in a graphene field-effect aptasensor

Biosensors based on graphene field-effect transistors have become a promising tool for detecting a broad range of analytes. However, their performance is substantially affected by the functionalization protocol. In this work, we use a controlled in-vacuum physical method for the covalent functionalization of graphene to construct ultrasensitive aptamer-based biosensors (aptasensors) able to detect hepatitis C virus core protein. These devices are highly specific and robust, achieving attomolar detection of the viral protein in human blood plasma. Such an improved sensitivity is rationalized by theoretical calculations showing that induced polarization at the graphene interface, caused by the proximity of covalently bound molecular probe, modulates the charge balance at the graphene/aptamer interface. This charge balance causes a net shift of the Dirac cone providing enhanced sensitivity for the attomolar detection of the target proteins. Such an unexpected effect paves the way for using this kind of graphene-based functionalized platforms for ultrasensitive and real-time diagnostics of different diseases.EU Graphene Flagship funding (Grant Graphene Core3 881603), the Ministerio de Ciencia e Innovación of Spain: PID2020-113142RB-C21, the European Structural Funds via FotoArt-CM project (P2018/NMT-4367) and the Portuguese Foundation for Science and Technology (FCT) via the Strategic Funding UIDB/04650/2020. Work at CAB was funded by the Spanish Ministerio de Ciencia e Innovación (MICINN) grant no. PID2019-104903RB-I00 and the Spanish Agencia Estatal de Investigación (AEI) Project no. MDM-2017-0737 - Unidad de Excelencia “María de Maeztu,” and it also benefits from the interdisciplinary framework provided by CSIC through “LifeHUB.CSIC” initiative (PIE 202120E047-CONEXIONES-LIFE). CIBERehd is funded by Instituto de Salud Carlos III (ISCIII). A.N. is supported by the predoctoral fellowship PRE-CAB-BIOMOLECULAS 2 from INTA. B.T-V. is supported by the predoctoral fellowship TS17/16 from INTA and by the CSIC “Garantía Juvenil” contract CAM19_PRE_CAB_001 funded by Comunidad de Madrid (CAM). FCT supports T.D. and P.C. under Ph.D. grants SFRH/BD/08181/2020 and SFRH/BD/128579/2017. M.M. would like to thank Comunidad de Madrid for the predoctoral grant IND2020/BIO-17523. P.A. and C.B. also acknowledge the support provided by La Caixa Foundation through Project LCF/PR/HR21/52410023. L. V. would like to thank Comunidad de Madrid (TRANSNANOAVANSENS program: S2018-NMT-4349) and E.V. García-Frutos for her assistance during the AFM experiments

Unveiling the collaborative effect at the cucurbit[8]urilMoS2 hybrid interface for electrochemical melatonin determination

Host-guest interactions are of paramount importance in supramolecular chemistry and in a wide range of applications. Particularly well known is the ability of cucurbit[n]urils (CB[n]) to selectively host small molecules. We show that the charge transfer and complexation capabilities of CB[n] are retained on the surface of 2D transition metal dichalcogenides (TMDs), allowing the development of efficient electrochemical sensing platforms. We unveil the mechanisms of host-guest recognition between the MoS2- CB[8] hybrid interface and melatonin (MLT), an important molecular regulator of vital constants in vertebrates. We find that CB[8] on MoS2 organizes the receptor portals perpendicularly to the surface, facilitating MLT complexation. This advantageous adsorption geometry is specific to TMDs and favours MLT electro-oxidation, as opposed to other 2D platforms like graphene, where one receptor portal is closed. This study rationalises the cooperative interaction in 2D hybrid systems to improve the efficiency and selectivity of electrochemical sensing platform

Tailoring \pi-conjugation and vibrational modes to steer on-surface synthesis of pentalene-bridged ladder polymers

The development of synthetic strategies to engineer \pi-conjugated polymers is of paramount importance in modern chemistry and materials science. Here we introduce a theoretical and experimental synthetic paradigm based on the search for specific vibrational modes through an appropriate tailoring of the \pi-conjugation of the precursors, in order to increase the attempt frequency of a chemical reaction. First, we on-surface design a 1D \pi-conjugated polymer with specific \pi-topology, which is based on bisanthene monomers linked by cumulene bridges that tune specific vibrational modes. In a second step, upon further annealing, such vibrational modes steer the two-fold cyclization reaction between adjacent bisanthene moieties, which gives rise to a long and free-defect pentalene-bridged conjugated ladder polymer featuring a low band gap. In addition, high resolution atomic force microscopy allows us to identify by atomistic insights the resonant form of the polymer, thus confirming the validity of the Glidewell and Lloyd's rules for aromaticity. This on-surface synthetic strategy may stimulate exploiting previously precluded reactions towards novel pi-conjugated polymers with specific structures and properties