{"id":570,"date":"2021-06-30T12:00:33","date_gmt":"2021-06-30T12:00:33","guid":{"rendered":"https:\/\/admin.acceleratingscience.com\/atomic-resolution\/2021\/06\/30\/expedited-cryo-em-structure-based-drug-design\/"},"modified":"2022-12-01T18:48:47","modified_gmt":"2022-12-01T18:48:47","slug":"expedited-cryo-em-structure-based-drug-design","status":"publish","type":"post","link":"https:\/\/www.thermofisher.com\/blog\/atomic-resolution\/expedited-cryo-em-structure-based-drug-design\/","title":{"rendered":"Expedited Cryo-EM Structure-Based Drug Design: From Gene to Novel Chemistry"},"content":{"rendered":"

Structure-based drug design involves uncovering the three-dimensional structure of therapeutically relevant targets for drug discovery and development.<\/p>\n

Compared to ligand-based methods, this type of drug design can accelerate the development process and make it possible to precisely design small molecules that either bring out or suppress a response in the human body.<\/p>\n

Historically, X-ray crystallography was a critical part of structure-based drug design and resulted in the development of potent inhibitors for the treatment of a wide variety of diseases from AIDS to cancer.<\/p>\n

Yet, due to the limits of this technique, many important drug targets\u2014including macromolecular assemblies and membrane proteins\u2014were left out of structure-based drug design efforts.<\/p>\n

The good news is that recent advances in protein production, coupled with the increasingly popular cryo-electron microscopy (cryo-EM) technique, are expanding the role of structure-based drug design for these critical targets.<\/p>\n

Modern structure-based drug design: a case study<\/strong><\/h2>\n

Using cryo-EM in combination with computational chemistry methods, researchers are poised to revolutionize structure-based drug design, which could lead to highly precise drugs that target a wider range of debilitating diseases. In other words, better drugs in less time.<\/p>\n

\"Expedited<\/p>\n

Using Thermo Fisher Scientific’s gene-to-protein and cryo-EM solutions, in combination with the <\/em>Schr\u00f6dinger<\/em>\u00a0platform, it is possible to get from gene to novel, computationally designed small molecules in just three months.<\/em><\/p>\n

To demonstrate the potential of cryo-EM in the structure-based drug design process<\/a>, Thermo Fisher Scientific collaborated with Schr\u00f6dinger to create a white paper showcasing the expedited gene-to-drug approach, finding hits in only three months.<\/a> To do so, they utilized Thermo Fisher\u2019s high-powered cryo-EM solutions and Invitrogen GeneArt Gene-to-Protein Services in combination with the Schr\u00f6dinger\u00a0<\/strong>Drug Discovery platform<\/a>.<\/strong><\/p>\n

An expedited gene-to-drug approach<\/strong><\/h2>\n

Selection of targets for initiation of drug discovery depends on understanding the unmet medical need of focus, and evidence from clinical, genetic and preclinical studies inform therapeutic potential.<\/p>\n

According to the collaborators in this study, \u201cAll targets must be modeling enabled for structure-based drug design\u2026The Schr\u00f6dinger platform is used to analyze protein structure quality and binding site druggability, followed by an assessment of the amenability of the structures for use with the technology. Due to the lack of high-quality structures…[many] interesting targets that meet the criteria for biological rationale and therapeutic momentum need to be discarded. This is often because such targets are…often challenging for X-ray crystallography. Fortunately, these types of targets are often well suited for structural determination by cryo-EM and allow for modelling of previously unreachable targets.\u201d<\/p>\n