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Biology subjects

Goodsell, D. S.

Publications and source records attributed to Goodsell, D. S..

2 recordsLinked to original sources

Mesoscale Explorer - Visual Exploration of Large-Scale Molecular Models

The advent of cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), coupled with computational modeling, has enabled the creation of integrative 3D models of viruses, bacteria, and cellular organelles. These models, composed of thousands of macromolecules and billions of atoms, have historically posed significant challenges for manipulation and visualization without specialized molecular graphics tools and hardware. With the recent advancements in GPU rendering power and web browser capabilities, it is now feasible to render interactively large molecular scenes directly on the web. In this work, we introduce Mesoscale Explorer, a web application built using the Mol* framework, dedicated to the visualization of large-scale molecular models ranging from viruses to cell organelles. Mesoscale Explorer provides unprecedented access and insight into the molecular fabric of life, enhancing perception, streamlining exploration, and simplifying visualization of diverse data types, showcasing the intricate details of these models with unparalleled clarity. Statement: Mesoscale Explorer leverages advanced GPU rendering and web technologies to facilitate and democratize the interactive 3D visualization of large-scale molecular models from viruses to cellular organelles composed of millions of atoms. Mesoscale Explorer enables broader exploration and deeper understanding of the complex structure of these large molecular landscapes.

bioinformatics↗

Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first six months of the COVID-19 pandemic

Three-dimensional structures of SARS-CoV-2 and other coronaviral proteins archived in the Protein Data Bank were used to analyze viral proteome evolution during the first six months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48,000 viral proteome sequences showed how each one of the 29 viral study proteins have undergone amino acid changes. Structural models computed for every unique sequence variant revealed that most substitutions map to protein surfaces and boundary layers with a minority affecting hydrophobic cores. Conservative changes were observed more frequently in cores versus boundary layers/surfaces. Active sites and protein-protein interfaces showed modest numbers of substitutions. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Detailed results are presented for six drug discovery targets and four structural proteins comprising the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and functional interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.

molecular biology↗