Biochemistry and Pharmacology - Research Publications

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    COVID-3D: An online resource to explore the structural distribution of genetic variation in SARS-CoV-2 and its implication on therapeutic development
    Portelli, S ; Olshansky, M ; Rodrigues, CHM ; D’Souza, E ; Myung, Y ; Silk, M ; Alavi, A ; Pires, DEV ; Ascher, D (Cold Spring Harbor Laboratory, 2020)


    The emergence of the COVID-19 pandemic has spurred a global rush to uncover basic biological mechanisms, to inform effective vaccine and drug development. Despite viral novelty, global sequencing efforts have already identified genomic variation across isolates. To enable easy exploration and spatial visualization of the potential implications of SARS-CoV-2 mutations on infection, host immunity and drug development we have developed COVID-3D ( ).
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    ENRICH: a fast method to improve the quality of flexible macromolecular reconstructions
    Kazemi, M ; Sorzano, COS ; Des Georges, A ; Carazo, JM ; Vargas, J (Cold Spring Harbor Laboratory, 2018)
    Cryo-electron microscopy using single particle analysis requires the computational averaging of thousands of projection images captured from identical macromolecules. However, macromolecules usually present some degree of flexibility showing different conformations. Computational approaches are then required to classify heterogeneous single particle images into homogeneous sets corresponding to different structural states. Nonetheless, sometimes the attainable resolution of reconstructions obtained from these smaller homogeneous sets is compromised because of reduced number of particles or lack of images at certain macromolecular orientations. In these situations, the current solution to improve map resolution is returning to the electron microscope and collect more data. In this work, we present a fast approach to partially overcome this limitation for heterogeneous data sets. Our method is based on deforming and then moving particles between different conformations using an optical flow approach. Particles are then merged into a unique conformation obtaining reconstructions with improved resolution, contrast and signal-to-noise ratio, then, partially circumventing many issues that impact obtaining high quality reconstructions from small data sets. We present experimental results that show clear improvements in the quality of obtained 3D maps, however, there are also limits to this approach, which we discuss in the manuscript.