COVID MOONSHOT SPRINT 11: The home stretch
Rev up your GPUs and help us in the final stretch of nominating a patent-free oral antiviral for preclinical studies!
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Editorial: Experiments and Simulations: A Pas de Deux to Unravel Biological Function
In a new Editorial, Folding@home Director Greg Bowman and collaborators explain how simulation and experiment can work together to illuminate the detailed mechanisms of biology and disease.
Read moreEquilibrium fluctuations of a single folded protein reveal a multitude of potential cryptic allosteric sites
A new paper from the Bowman lab proposes that potentially druggable cryptic allosteric sites may be even more ubiquitous than previously thought, and that our new simulation methods should be a valuable means of guiding the search for such sites.
Read moreClassic paper: Improved coarse-graining of Markov state models via explicit consideration of statistical uncertainty
This classic paper from Folding@home Director Greg Bowman describes a Bayesian approach to clustering microstates into metastable states for building Markov state models, a foundational Folding@home technology.
Read moreCirculating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity
Folding@home helps experimental collaborators understand mutations that drive increased fitness of SARS-CoV-2 mutants.
Read moreAntibodies to the SARS-CoV-2 receptor-binding domain that maximize breadth and resistance to viral escape
An ideal anti-SARS-CoV-2 antibody would resist viral escape 1-3 , have activity against diverse SARS-related coronaviruses 4-7 , and be highly protective through viral neutralization 8-11 and effector functions 12,13 . Understanding how these properties relate to each other and vary across epitopes would aid development of antibody therapeutics and guide vaccine design…
Read moreWhat Markov State Models Can and Cannot Do: Correlation versus Path-Based Observables in Protein-Folding Models
Markov state models (MSMs) have been widely applied to study the kinetics and pathways of protein conformational dynamics based on statistical analysis of molecular dynamics (MD) simulations. These MSMs coarse-grain both configuration space and time in ways that limit what kinds of observables they can reproduce with high fidelity over different spatial and te…
Read moreDiscovery of SARS-CoV-2 main protease inhibitors using a synthesis-directed de novo design model
The SARS-CoV-2 main viral protease (Mpro) is an attractive target for antivirals given its distinctiveness from host proteases, essentiality in the viral life cycle and conservation across coronaviridae. We launched the COVID Moonshot initiative to rapidly develop patent-free antivirals with open science and open data. Here we report the use of machine learnin…
Read moreSARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape
An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape1-3, have activity against diverse sarbecoviruses4-7, and be highly protective through viral neutralization8-11 and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid the development…
Read moreBest Practices for Alchemical Free Energy Calculations [Article v1.0]
Alchemical free energy calculations are a useful tool for predicting free energy differences associated with the transfer of molecules from one environment to another. The hallmark of these methods is the use of “bridging” potential energy functions representing alchemical intermediate states that cannot exist as real chemical species. The data collecte…
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