Representability of algebraic topology for biomolecules in machine learning based scoring and virtual screening

This work introduces a number of algebraic topology approaches, such as multicomponent persistent homology, multi-level persistent homology and electrostatic persistence for the representation, characterization, and description of small molecules and biomolecular complexes. Multicomponent persistent homology retains critical chemical and biological information during the topological simplification of biomolecular geometric complexity. Multi-level persistent homology enables a tailored topological description of inter- and/or intra-molecular interactions of interest. Electrostatic persistence incorporates partial charge information into topological invariants. These topological methods are paired with Wasserstein distance to characterize similarities between molecules and are further integrated with a variety of machine learning algorithms, including k-nearest neighbors, ensemble of trees, and deep convolutional neural networks, to manifest their descriptive and predictive powers for chemical and biological problems. Extensive numerical experiments involving more than 4,000 protein-ligand complexes from the PDBBind database and near 100,000 ligands and decoys in the DUD database are performed to test respectively the scoring power and the virtual screening power of the proposed topological approaches. It is demonstrated that the present approaches outperform the modern machine learning based methods in protein-ligand binding affinity predictions and ligand-decoy discrimination

Towards defining the role of glycans as hardware in information storage and transfer: Basic principles, experimental approaches and recent progress

The term `code' in biological information transfer appears to be tightly and hitherto exclusively connected with the genetic code based on nucleotides and translated into functional activities via proteins. However, the recent appreciation of the enormous coding capacity of oligosaccharide chains of natural glycoconjugates has spurred to give heed to a new concept: versatile glycan assembly by the genetically encoded glycosyltransferases endows cells with a probably not yet fully catalogued array of meaningful messages. Enciphered by sugar receptors such as endogenous lectins the information of code words established by a series of covalently linked monosaccharides as fetters for example guides correct intra- and intercellular routing of glycoproteins, modulates cell proliferation or migration and mediates cell adhesion. Evidently, the elucidation of the structural frameworks and the recognition strategies within the operation of the sugar code poses a fascinating conundrum. The far-reaching impact of this recognition mode on the level of cells, tissues and organs has fueled vigorous investigations to probe the subtleties of protein-carbohydrate interactions. This review presents information on the necessarily concerted approach using X-ray crystallography, molecular modeling, nuclear magnetic resonance spectroscopy, thermodynamic analysis and engineered ligands and receptors. This part of the treatise is flanked by exemplarily chosen insights made possible by these techniques. Copyright (C) 2001 S. Karger AG, Basel

Hydrogen Isotope Transport and Separation via Layered and Two-Dimensional Materials

The enrichment of heavy hydrogen isotopes (deuterium, tritium) is required to fulfill their increasing application demands, e.g., in isotope related tracing, cancer therapy and nuclear reaction plants. However, their exceedingly low natural abundance and the close resemblance of physiochemical properties to protium render them extremely difficult to be separated. In this thesis, we investigate hydrogen isotope transport and separation via layered and two-dimensional materials. Three different theoretical challenges are undertaken in this work: (1) identification of the transported hydrogen species (proton H+ or protium H atom) inside interstitial space of layered materials (hexagonal boron nitride, molybdenum disulfide and graphite) and elucidation of their transport mechanism; (2) separation of hydron (proton H+, deuteron D+, and triton T+) isotopes through vacancy-free graphene and hexagonal boron nitride monolayers; (3) capture of the extremely rare light helium isotope (3He) with atomically thin two-dimensional materials. In the case of hydrogen transport, the essential challenges are investigation of its mechanism as well as the identification of transported particles. Regarding the case of hydron isotope separation, the essential questions are whether or not pristine graphene is permeable to the isotopes, and how quantum tunneling and topological Stone-Wales 55-77 defects affect their permeation and separation through graphene. In the last case, to capture the light helium isotope, quantum tunneling, which favors the lighter particles, is utilized to harvest 3He using graphdiyne monolayer. Our results provide novel theoretical insights into hydrogen particle transport inside the interstitial space of van der Waals materials; they uncover the mechanism of hydron isotope separation through 2D graphene and hexagonal boron nitride monolayers; and they predict the influence of pure quantum tunneling on the enrichment of 3He through graphdiyne membrane

First Principles Investigations of Novel Condensed Matter Materials

The advent of very fast computing power has led to the positioning of theoretical investigations of condensed matter materials as a core part of research in this area. Often the results of such numerical and computational investigations serve as reliable guide for future experimental exploration of new materials and has led to the discovery of numerous materials. In this thesis, state-of-the-art first principles calculations have been applied to investigate the structural, electronic and dynamical properties of some novel condensed matter materials. The novelty of these compounds stems from the fact that they challenge our previous knowledge of the chemistry of chemical reactions that support the formation and stability of chemical compounds and can therefore expand our frontier of knowledge in the quest for scientific understanding of new atypical compounds in high pressure physics. In the first project, the long sought post-Cmcm phase of the cadmium telluride is characterized with the application of first principles metadynamics method. It has a monoclinic unit cell and the P21/m space group. Enthalpy calculation confirms this phase transition sequence and further predicts a P21/m to P4/nmm transition near 68 GPa. Interestingly, the enthalpies of CdTe compounds are found to be higher than the enthalpy sum of its constituents Cd and Te at pressures higher than 34 GPa which is an indication that the com-pound should decompose above this pressure point. However, dynamical stability revealed in the phonon dispersion relations prevents the decomposition of CdTe at high pressure. This suggests that CdTe becomes a high-enthalpy compound at high pressure. The second project is directed towards the prediction of stable helium-hydrogen compound. In spite of extensive experimental and theoretical work, a general agreement on the crystal structure and stability of the helium-hydrogen system is lacking. In this study, the possibility of helium forming stable compound with hydrogen is investigated by using first principles structure search method. A stable helium hydrogen compound formed at ambient conditions is found. It belongs to the triclinic P-1 space group, having He(H2)3stoichiometry. Topological analysis of electron density at the bond critical points shows there exists a quantifiable level of bonding interaction between helium and hydrogen in the P-1 structure. At ambient pressure, the compound is characterized and stabilized by interactions with strength typical of van der Waals interaction that increases with pressure. This current results provide a case of weak interaction in a mixed hydrogen-helium system, offering insights for the evolution of interiors of giant planets such as Jupiter and Saturn. In the final project, a machine learning potential is successfully created for sodium based on the Gaussian process regression method and weighted atom-centered symmetry functions representation of the potential energy surface. Here, sodium potential energy surface is described using different relevant data sets that represent several regions of the potential energy surface with each data set consisting of three element groups which are total energies, inter-atomic forces, and stress tensors of the cell, which were constructed from density functional theory calculations. It is demonstrated that by learning from the underlying density functional theory results, the trained machine learning potential is able to reproduce important properties of all available sodium phases with an exceptional accuracy in comparison to those computed using density functional theory. In combination with the metadynamics method, this well trained machine learning potential is applied to large simulation boxes containing1024 and 3456 sodium atoms in the cI16 phase. These large-scale simulations reveal a notable phase transition at 150 K and 120 GPa with an impressive capturing of the rearrangements of atomic configurations involved in the transition process that may not be evident in asmall-scale simulation. Without a doubt, this work shows that applying machine learning methods to condensed matter systems will lead to significant increase in our understanding of important processes such as atomic rearrangements, growth and nucleation process in crystal formation and phase transition

The hydrogen bond: a molecular beam microwave spectroscopist's view with a universal appeal

In this manuscript, we propose a criterion for a weakly bound complex formed in a supersonic beam to be characterized as a 'hydrogen bonded complex'. For a 'hydrogen bonded complex', the zero point energy along any large amplitude vibrational coordinate that destroys the orientational preference for the hydrogen bond should be significantly below the barrier along that coordinate so that there is at least one bound level. These are vibrational modes that do not lead to the breakdown of the complex as a whole. If the zero point level is higher than the barrier, the 'hydrogen bond' would not be able to stabilize the orientation which favors it and it is no longer sensible to characterize a complex as hydrogen bonded. Four complexes, Ar2-H2O, Ar2-H2S, C2H4-H2O and C2H4-H2S, were chosen for investigations. Zero point energies and barriers for large amplitude motions were calculated at a reasonable level of calculation, MP2(full)/aug-cc-pVTZ, for all these complexes. Atoms in molecules (AIM) theoretical analyses of these complexes were carried out as well. All these complexes would be considered hydrogen bonded according to the AIM theoretical criteria suggested by Koch and Popelier for C-H···O hydrogen bonds (U. Koch and P. L. A. Popelier, J. Phys. Chem., 1995, 99, 9747), which has been widely and, at times, incorrectly used for all types of contacts involving H. It is shown that, according to the criterion proposed here, the Ar2-H2O/H2S complexes are not hydrogen bonded even at zero kelvin and C2H4-H2O/H2S complexes are. This analysis can naturally be extended to all temperatures. It can explain the recent experimental observations on crystal structures of H2S at various conditions and the crossed beam scattering studies on rare gases with H2O and H2S

Probing the magnetism of topological end states in 5-armchair graphene nanoribbons

We extensively characterize the electronic structure of ultranarrow graphene nanoribbons (GNRs) with armchair edges and zigzag termini that have five carbon atoms across their width (5-AGNRs), as synthesized on Au(111). Scanning tunneling spectroscopy measurements on the ribbons, recorded on both the metallic substrate and a decoupling NaCl layer, show well-defined dispersive bands and in-gap states. In combination with theoretical calculations, we show how these in-gap states are topological in nature and localized at the zigzag termini of the nanoribbons. In addition to rationalizing the driving force behind the topological class selection of 5-AGNRs, we also uncover the length-dependent behavior of these end states which transition from singly occupied spin-split states to a closed-shell form as the ribbons become shorter. Finally, we demonstrate the magnetic character of the end states via transport experiments in a model two-terminal device structure in which the ribbons are suspended between the scanning probe and the substrate that both act as leads.We acknowledge funding from the European Union’s Horizon 2020 programme (Grant Agreement Nos. 635919 and 863098 from ERC and FET Open projects, respectively), from the Spanish MINECO (Grant Nos. FIS2017-83780-P and MAT2016-78293-C6), and from the University of the Basque Country (Grant IT1246-19). D.G.O. thanks the Alexander von Humboldt Foundation for supporting his research stay at the MPI, and Klaus Kern for hosting him.Peer reviewe