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Biology subjects

Harris, S. F.

Publications and source records attributed to Harris, S. F..

2 recordsLinked to original sources

GYDE: A collaborative drug discovery platform for AI-powered protein design and engineering

As computational tools and machine learning models for protein sciences continue to advance and proliferate, bench scientists face increasing technical challenges adopting these tools for specific applications such as drug discovery. Here we present GYDE (Guide Your Design and Engineering), an open-source, versatile, and web-based collaboration platform designed to make computational analyses of proteins and antibodies easily accessible to bench scientists. GYDE enables the exploration of sequence-structure-function relationships through a tightly integrated visual interface, offering researchers a comprehensive exploration of protein functional determinants either via real assay data or computational tools. GYDEs intuitive interface facilitates seamless access to cutting-edge AI models for protein and antibody structure prediction, design, and downstream analyses. The flexible and easy addition of new tools and models is facilitated by the use of the Slivka compute API. The platform supports saved sessions that enable researchers to easily share their findings with other users, fostering a more collaborative scientific community. GYDE is freely available for protein scientists in academia and industry to build drug discovery analytics platforms customized to their needs.

bioinformatics↗

Novel Antibody Interfaces Revealed Through Structural Mining

Antibodies are fundamental effectors of humoral immunity, and have become a highly successful class of therapeutics. There is increasing evidence that antibodies utilize transient homotypic interactions to enhance function, and elucidation of such interactions can provide insights into their biology and new opportunities for their optimization as drugs. Yet the transitory nature of weak interactions makes them difficult to investigate. Capitalizing on their rich structural data and high conservation, we have characterized all the ways that antibody Fab regions interact crystallographically. This approach led to the discovery of previously unrealized interfaces between antibodies. While diverse interactions exist, {beta}-sheet dimers and variable-constant elbow dimers are recurrent motifs. Disulfide engineering enabled interactions to be trapped and investigated structurally and functionally, providing experimental validation of the interfaces and illustrating their potential for optimization. This work provides first insight into previously undiscovered oligomeric interactions between antibodies, and enables new opportunities for their biotherapeutic optimization.

biochemistry↗