Identification of Ligand Binding Sites of Proteins Using the Gaussian Network Model

The nonlocal nature of the protein-ligand binding problem is investigated via the Gaussian Network Model with which the residues lying along interaction pathways in a protein and the residues at the binding site are predicted. The predictions of the binding site residues are verified by using several benchmark systems where the topology of the unbound protein and the bound protein-ligand complex are known. Predictions are made on the unbound protein. Agreement of results with the bound complexes indicates that the information for binding resides in the unbound protein. Cliques that consist of three or more residues that are far apart along the primary structure but are in contact in the folded structure are shown to be important determinants of the binding problem. Comparison with known structures shows that the predictive capability of the method is significant

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

The elastic behaviour of orthorhombic sulphur under pressure

Orthorhombic, alpha-sulphur comprises rings strongly bound by covalent, intramolecular forces but held together by much weaker intermolecular bonds. To examine the vibrational anharmonicity of the long-wavelength acoustic modes in a molecular crystal of this type, the effects of hydrostatic and uniaxial pressures upon the velocities of ultrasonic modes propagated in a single crystal of orthorhombic sulphur have been measured. From the experimental results at room temperature 19 of 20 third-order elastic constants and also the hydrostatic pressure derivatives of the 9 second-order elastic constants have been obtained. The elastic stiffnesses and their hydrostatic pressure derivatives have also been calculated from an intermolecular potential of the 6-exp variety. Good agreement between the results obtained from this lattice dynamical calculation and the ultrasonic experiments establishes that the potential model provides a reasonable description of the elastic behaviour of this molecular crystal. The compression estimated from the Murnaghan equation of state agrees well with that estimated theoretically from the lattice dynamic calculations. The Debye temperature determined from the ultrasonic-wave velocities is 187.5 \pm. Ultrasonic-wave velocities are linear up to about 100C; the crystals do not undergo the transition to a monoclinic phase which can take place at 95C. There is no indication of softening of the long-wavelength acoustic phonon modes. Vibrational anharmonicity is discussed in terms of the long-wavelength acoustic-mode Gruneisen parameters obtained from the generalized Gruneisen theory in the quasiharmonic approximation. The mean high-temperature long-wavelength acoustic-mode Gruneisen parameter (= 2.72) is much larger than the room-temperature thermal Gruneisen parameter (= 0.54). In this molecular crystal the intermolecular volume is much more compressible than the intramolecular volume; the mode Gruneisen parameters for purely internal vibrational modes are small, whereas those for the external modes are large. At room temperature all phonon modes contribute so that is made small by the small internal-mode contributions. In contrast, the weak, strongly pressure dependent intermolecular forces dominate the zone-centre acoustic modes and lead to a large mean Gruneisen parameter

Exploring Protein Conformational Diversity

The native state of proteins is composed of conformers in dynamical equilibrium. In this chapter, different issues related to conformational diversity are explored using a curated and experimentally based database called CoDNaS (Conformational Diversity in the Native State). This database is a collection of redundant structures for the same sequence. CoDNaS estimates the degree of conformational diversity using different global and local structural similarity measures. It allows the user to explore how structural differences among conformers change as a function of several structural features providing further biological information. This chapter explores the measurement of conformational diversity and its relationship with sequence divergence. Also, it discusses how proteins with high conformational diversity could affect homology modeling techniques.Fil: Monzon, Alexander Miguel. Universidad Nacional de Quilmes; ArgentinaFil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zea, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; ArgentinaFil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentin