Chemical Computing Group

Hey All, The wonderful folks over at CCG invited me to be a guest on their podcast "Under the Surface" Check it out! :)

[𝗣𝗢𝗗𝗖𝗔𝗦𝗧] Check out the next episode of our podcast, 𝗨𝗻𝗱𝗲𝗿 𝘁𝗵𝗲 𝗦𝘂𝗿𝗳𝗮𝗰𝗲! 𝗜𝗻 𝗲𝗽𝗶𝘀𝗼𝗱𝗲 9, 𝙍𝙚𝙗𝙚𝙘𝙘𝙖 𝙎𝙬𝙚𝙩𝙩 𝙤𝙣 𝙏𝙝𝙚 𝙋𝙤𝙬𝙚𝙧 𝙤𝙛 𝘼𝙪𝙩𝙤𝙢𝙖𝙩𝙞𝙤𝙣 𝙞𝙣 𝘿𝙧𝙪𝙜 𝘿𝙚𝙫𝙚𝙡𝙤𝙥𝙢𝙚𝙣𝙩, in our final episode of 2024, host Chris Williams and guest co-host, Under the Surface Executive Producer and CCG Vice President, Alain Deschênes have a long overdue chat with computational drug discovery rock star Rebecca Swett. Rebecca shares her journey from her academic beginnings to her current role at X-Chem, via roles at Novartis, Vertex, and Relay. Rebecca’s wide-ranging experience shines through as the conversation wends its way through cutting-edge computational chemistry covering machine learning, molecular dynamics, and DNA-encoded libraries. At the scale Rebecca works at, automation is key, so this topic comes up too. We’re not going to lie; it’s a lot. And, of course, there’s more … Rebecca highlights the significance of allyship and representation for women in science, and the role of community (with a shout-out to the long-running BAGIM modeling forum). Also, in the inaugural asking of the ‘Deschênes Dilemma,’ we find out what Rebecca would be doing if she wasn’t doing all of the above … To listen to this episode, visit https://bit.ly/3WQGPKY Also available on Apple, Spotify, or wherever you get your podcasts. #DrugDiscovery #CADD #DrugDesign #CompChem #MachineLearning #DNAEncodedLibraries

Wishing you a Happy Holiday season from all of us at CCG. Cheers for the New Year! 🎊 🥳 🎉

[𝗖𝗼𝗻𝗳𝗲𝗿𝗲𝗻𝗰𝗲] We're thrilled to announce our participation in the 𝗔𝗻𝘁𝗶𝗯𝗼𝗱𝘆 𝗘𝗻𝗴𝗶𝗻𝗲𝗲𝗿𝗶𝗻𝗴 𝗮𝗻𝗱 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰𝘀 2024 conference, taking place December 15–19 in San Diego! Visit us at Booth #112 to explore our latest advancements in biologics, including antibody modeling and protein engineering. For event details, please visit: https://bit.ly/3uUNavc Our Poster Presentations: 𝗦𝘁𝗿𝘂𝗰𝘁𝘂𝗿𝗲-𝗕𝗮𝘀𝗲𝗱 𝗖𝗵𝗮𝗿𝗴𝗲 𝗖𝗮𝗹𝗰𝘂𝗹𝗮𝘁𝗶𝗼𝗻𝘀 𝗳𝗼𝗿 𝗣𝗿𝗲𝗱𝗶𝗰𝘁𝗶𝗻𝗴 𝗣𝗿𝗼𝗽𝗲𝗿𝘁𝗶𝗲𝘀 𝗮𝗻𝗱 𝗣𝗿𝗼𝗳𝗶𝗹𝗶𝗻𝗴 𝗔𝗻𝘁𝗶𝗯𝗼𝗱𝘆 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰𝘀 We present a method for modeling antibodies and performing pH-dependent conformational sampling, which can enhance property calculations. Structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich those that are approved by the U.S. Food and Drug Administration (FDA). 𝗖𝗿𝗲𝗮𝘁𝗶𝗻𝗴 𝗙𝗼𝗰𝘂𝘀𝗲𝗱 𝗟𝗶𝗯𝗿𝗮𝗿𝗶𝗲𝘀 𝗳𝗼𝗿 𝗣𝗿𝗼𝘁𝗲𝗶𝗻 𝗘𝗻𝗴𝗶𝗻𝗲𝗲𝗿𝗶𝗻𝗴 Protein engineering plays a pivotal role in modulating the function, activity and physical properties of biologics. Representative strategies employed in protein engineering include rational protein design and directed evolution. When the sequence design space is too large, multiple experiments must be conducted to enable an efficient and complete search. Ideally, a priori knowledge can be used to reduce this space by mutating residues that have higher probabilities of yielding a bio-therapeutic with the desired protein properties. When this knowledge is lacking, one can turn to computer-aided biologics design (CABD) techniques to garner information about a potential bio-therapeutic and its properties. Here we establish a method for predicting mutation probabilities, in order to reduce the number of variants in a given library. #DrugDiscovery #CADD #Biologics #AntibodyModeling #Developability #ProteinEngineering

[𝗖𝗼𝗻𝗳𝗲𝗿𝗲𝗻𝗰𝗲] We're thrilled to announce our participation in the 𝗔𝗻𝘁𝗶𝗯𝗼𝗱𝘆 𝗘𝗻𝗴𝗶𝗻𝗲𝗲𝗿𝗶𝗻𝗴 𝗮𝗻𝗱 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰𝘀 2024 conference, taking place December 15–19 in San Diego! Visit us at Booth #112 to explore our latest advancements in biologics, including antibody modeling and protein engineering. For event details, please visit: https://bit.ly/3uUNavc Our Poster Presentations: 𝗦𝘁𝗿𝘂𝗰𝘁𝘂𝗿𝗲-𝗕𝗮𝘀𝗲𝗱 𝗖𝗵𝗮𝗿𝗴𝗲 𝗖𝗮𝗹𝗰𝘂𝗹𝗮𝘁𝗶𝗼𝗻𝘀 𝗳𝗼𝗿 𝗣𝗿𝗲𝗱𝗶𝗰𝘁𝗶𝗻𝗴 𝗣𝗿𝗼𝗽𝗲𝗿𝘁𝗶𝗲𝘀 𝗮𝗻𝗱 𝗣𝗿𝗼𝗳𝗶𝗹𝗶𝗻𝗴 𝗔𝗻𝘁𝗶𝗯𝗼𝗱𝘆 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰𝘀 We present a method for modeling antibodies and performing pH-dependent conformational sampling, which can enhance property calculations. Structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich those that are approved by the U.S. Food and Drug Administration (FDA). 𝗖𝗿𝗲𝗮𝘁𝗶𝗻𝗴 𝗙𝗼𝗰𝘂𝘀𝗲𝗱 𝗟𝗶𝗯𝗿𝗮𝗿𝗶𝗲𝘀 𝗳𝗼𝗿 𝗣𝗿𝗼𝘁𝗲𝗶𝗻 𝗘𝗻𝗴𝗶𝗻𝗲𝗲𝗿𝗶𝗻𝗴 Protein engineering plays a pivotal role in modulating the function, activity and physical properties of biologics. Representative strategies employed in protein engineering include rational protein design and directed evolution. When the sequence design space is too large, multiple experiments must be conducted to enable an efficient and complete search. Ideally, a priori knowledge can be used to reduce this space by mutating residues that have higher probabilities of yielding a bio-therapeutic with the desired protein properties. When this knowledge is lacking, one can turn to computer-aided biologics design (CABD) techniques to garner information about a potential bio-therapeutic and its properties. Here we establish a method for predicting mutation probabilities, in order to reduce the number of variants in a given library. #DrugDiscovery #CADD #Biologics #AntibodyModeling #Developability #ProteinEngineering

[This Week] Join us for our upcoming webinar, 𝗡𝗲𝘄 𝗮𝗻𝗱 𝗘𝗻𝗵𝗮𝗻𝗰𝗲𝗱 𝗕𝗶𝗼𝗹𝗼𝗴𝗶𝗰𝘀 𝗙𝗲𝗮𝘁𝘂𝗿𝗲𝘀 𝗶𝗻 𝗠𝗢𝗘 2024.06, on November 12 at 11:00 AM EST. Discover the latest features and enhancements in MOE 2024.06 for biologics applications. For more information and to register, please visit https://lnkd.in/eFdpDWi3 DATE: Tuesday, November 12, 2024 TIME: 11:00-11:45 Boston Time / 16:00-16:45 London Time TAGS: Antibody Modeling / Capture Design Ideas / Antibody Pharmacophore Virtual Screening / Interactive Database Viewer Property Filter / Protein Docking Validation / Map 2D Protein Patch Differences / Visualize Ensemble Averages #DrugDesign #DrugDiscovery #CADD #Biologics #AntibodyModeling #ProteinEngineering #ProteinDocking

𝗖𝗼𝗻𝗳𝗲𝗿𝗲𝗻𝗰𝗲] We're excited to announce our participation at PEGS Europe 2024 in Barcelona, Spain! Join us at Booth #1204 to learn about our latest advancements in biologics applications, including antibody modeling and protein engineering. For more event details, visit: https://bit.ly/3shefYE Our Poster Presentations: 𝗦𝘁𝗿𝘂𝗰𝘁𝘂𝗿𝗲-𝗕𝗮𝘀𝗲𝗱 𝗖𝗵𝗮𝗿𝗴𝗲 𝗖𝗮𝗹𝗰𝘂𝗹𝗮𝘁𝗶𝗼𝗻𝘀 𝗳𝗼𝗿 𝗣𝗿𝗲𝗱𝗶𝗰𝘁𝗶𝗻𝗴 𝗣𝗿𝗼𝗽𝗲𝗿𝘁𝗶𝗲𝘀 𝗮𝗻𝗱 𝗣𝗿𝗼𝗳𝗶𝗹𝗶𝗻𝗴 𝗔𝗻𝘁𝗶𝗯𝗼𝗱𝘆 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰𝘀 We present a method for modeling antibodies and performing pH-dependent conformational sampling, which can enhance property calculations. Structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich those that are approved by the U.S. Food and Drug Administration (FDA). 𝗖𝗼𝗻𝘀𝘁𝗿𝗮𝗶𝗻𝗲𝗱 𝗣𝗲𝗽𝘁𝗶𝗱𝗲 𝗠𝗼𝗱𝗲𝗹𝗶𝗻𝗴, 𝗖𝗼𝗻𝗳𝗼𝗿𝗺𝗮𝘁𝗶𝗼𝗻𝗮𝗹 𝗔𝗻𝗮𝗹𝘆𝘀𝗶𝘀 𝗮𝗻𝗱 𝗣𝗿𝗼𝗽𝗲𝗿𝘁𝘆 𝗣𝗿𝗲𝗱𝗶𝗰𝘁𝗶𝗼𝗻𝘀 Peptides play an integral role in a myriad of biological pathways. Given their geometric and chemical diversity, peptides can effectively bind a broad spectrum of biological targets. This inherent diversity also presents numerous challenges such as the size of amino acid sequence space, assessment of low energy peptide conformational states and prediction of peptide properties. In this work, we present in silico methods for building peptide models, sampling peptide conformations and predicting the properties of peptides. #DrugDiscovery #CADD #Biologics #AntibodyModeling #Developability #ProteinEngineering #Peptides

[𝗖𝗼𝗻𝗳𝗲𝗿𝗲𝗻𝗰𝗲] Join us at the 18th German Conference on Cheminformatics in Bad Soden am Taunus (Booth B8), and attend our talk on 𝗡𝗼𝘃𝗲𝗹 𝗔𝗽𝗽𝗿𝗼𝗮𝗰𝗵𝗲𝘀 𝘁𝗼 𝗦𝗺𝗮𝗹𝗹 𝗠𝗼𝗹𝗲𝗰𝘂𝗹𝗲 𝗣𝗮𝗿𝗮𝗺𝗲𝘁𝗲𝗿𝗶𝘇𝗮𝘁𝗶𝗼𝗻. We’ll also be holding a workshop on 𝗚𝗲𝗻𝗲𝗿𝗮𝘁𝗶𝘃𝗲 𝗗𝗲𝘀𝗶𝗴𝗻 𝗼𝗳 𝗡𝗲𝘄 𝗖𝗮𝗻𝗱𝗶𝗱𝗮𝘁𝗲 𝗖𝗼𝗺𝗽𝗼𝘂𝗻𝗱𝘀 𝗶𝗻 𝘁𝗵𝗲 𝗕𝗶𝗻𝗱𝗶𝗻𝗴 𝗣𝗼𝗰𝗸𝗲𝘁 on Sunday, Nov 3, from 11:00-13:30. For more information, please visit https://bit.ly/3YBVIU1 𝗪𝗼𝗿𝗸𝘀𝗵𝗼𝗽: Sunday, 3 Nov 2024, 11:00 a.m. - Lecture Hall: Tolstoi 𝗚𝗲𝗻𝗲𝗿𝗮𝘁𝗶𝘃𝗲 𝗗𝗲𝘀𝗶𝗴𝗻 𝗼𝗳 𝗡𝗲𝘄 𝗖𝗮𝗻𝗱𝗶𝗱𝗮𝘁𝗲 𝗖𝗼𝗺𝗽𝗼𝘂𝗻𝗱𝘀 𝗶𝗻 𝘁𝗵𝗲 𝗕𝗶𝗻𝗱𝗶𝗻𝗴 𝗣𝗼𝗰𝗸𝗲𝘁 Presenters: Sarah Witzke and Guido Kirsten, Chemical Computing Group Computational methods can help plot potential ways forward in a lead optimisation campaign, starting from a ligand-bound crystal structure or a plausible computationally docked structure for a known active lead molecule. This workshop will demonstrate some of these methods using the Molecular Operating Environment (MOE) software system - culminating in an application to combinatorially enumerate, optimise, filter and assess compounds in the context of their binding site, given a real medicinal chemistry reaction and databases of reagents. 𝗧𝗮𝗹𝗸: Sunday, 3 Nov 2024, 04:00 p.m. - Lecture Hall: Mendelssohn 𝗔𝗺𝗯𝗲𝗿𝗘𝗛𝗧 𝗙𝗼𝗿𝗰𝗲𝗳𝗶𝗲𝗹𝗱: 𝗡𝗼𝘃𝗲𝗹 𝗔𝗽𝗽𝗿𝗼𝗮𝗰𝗵𝗲𝘀 𝘁𝗼 𝗦𝗺𝗮𝗹𝗹 𝗠𝗼𝗹𝗲𝗰𝘂𝗹𝗲 𝗣𝗮𝗿𝗮𝗺𝗲𝘁𝗲𝗿𝗶𝘇𝗮𝘁𝗶𝗼𝗻 Presenter: Sarah Witzke, Chemical Computing Group A new methodology to determine bonded forcefield parameters is presented. A coordinate-free Hückel calculation is the basis for chemical perception and the results are used in combination with physical chemistry relationships to determine parameters for bond lengths, angles and torsions (with associated force constants). Comparisons to quantum mechanical torsion profiles are presented to validate the resulting parameterizations. #DrugDiscovery #CADD #COMP

[𝗦𝘆𝗺𝗽𝗼𝘀𝗶𝘂𝗺] We had a great 𝗠𝗲𝗱𝗖𝗵𝗲𝗺 𝗯𝘆 𝗗𝗲𝘀𝗶𝗴𝗻 Europe 2024, Basel, symposium last week. On behalf of the Organizing Committee, a BIG thank you to all participants for their invaluable contributions, and a special thank you to our guest speakers for sharing their expertise and insights. We look forward to MedChem by Design Europe 2025! 𝗦𝗣𝗘𝗔𝗞𝗘𝗥𝗦: “In silico Approaches for Hit Identification and Optimization” 𝗔𝗻𝗻𝗮 𝗩𝘂𝗹𝗽𝗲𝘁𝘁𝗶, 𝗡𝗼𝘃𝗮𝗿𝘁𝗶𝘀 “Interpretable Data-Driven Medicinal Chemistry using BB-SAR” 𝗙𝗹𝗼𝗿𝗲𝗻𝘁 𝗖𝗵𝗲𝘃𝗶𝗹𝗹𝗮𝗿𝗱, 𝗜𝗱𝗼𝗿𝘀𝗶𝗮 𝗣𝗵𝗮𝗿𝗺𝗮𝗰𝗲𝘂𝘁𝗶𝗰𝗮𝗹𝘀 𝗟𝘁𝗱. “New Analogues for Top-Selling Drugs from Ultra-Large Combinatorial Libraries with 3D Pharmacophore Search (Pharos3D) 𝗠𝗼𝗱𝗲𝘀𝘁 𝘃𝗼𝗻 𝗞𝗼𝗿𝗳𝗳, 𝗔𝗹𝗶𝗽𝗵𝗲𝗿𝗼𝗻 𝗔𝗚” “MOEsaic: Guiding Multi-Parameter Optimization in Ligand-Based Design” 𝗔𝗻𝗱𝗿𝗲𝘄 𝗛𝗲𝗻𝗿𝘆, 𝗖𝗵𝗲𝗺𝗶𝗰𝗮𝗹 𝗖𝗼𝗺𝗽𝘂𝘁𝗶𝗻𝗴 𝗚𝗿𝗼𝘂𝗽 “Conformational Design of Inhibitors against PDE10 and MAGL” 𝗕𝗲𝗿𝗻𝗱 𝗞𝘂𝗵𝗻, 𝗙. 𝗛𝗼𝗳𝗳𝗺𝗮𝗻𝗻-𝗟𝗮 𝗥𝗼𝗰𝗵𝗲 𝗟𝘁𝗱. “Harnessing Computational Methods to Transform Oligosaccharides into Drug Leads: Tuning Conformational Pre-organization in E-selectin Antagonists” 𝗠𝗮𝗿𝘁𝗶𝗻 𝗦𝗺𝗶𝗲š𝗸𝗼, 𝗨𝗻𝗶𝘃𝗲𝗿𝘀𝗶𝘁𝘆 𝗼𝗳 𝗕𝗮𝘀𝗲𝗹 “Nonclassical Zwitterions as a Design Principle to Reduce Lipophilicity without Impacting Permeability” 𝗛𝗲𝗻𝗿𝗶𝗸 𝗠ö𝗯𝗶𝘁𝘇, 𝗡𝗼𝘃𝗮𝗿𝘁𝗶𝘀 “Rational Design Aided by Computation: From Covid Antivirals to Molecular Glues” 𝗩𝗹𝗮𝗱𝗮𝘀 𝗢𝗹𝗲𝗶𝗻𝗶𝗸𝗼𝘃𝗮𝘀, 𝗩𝗮𝗻𝘁𝗔𝗜 𝗢𝗥𝗚𝗔𝗡𝗜𝗭𝗘𝗥𝗦: Henrik Möbitz, Novartis Rainer Wilcken, Flare Therapeutics Steve Maginn, Chemical Computing Group Markus Kossner, Chemical Computing Group 𝗔𝗚𝗘𝗡𝗗𝗔 https://bit.ly/3Y81mgF #MedChem #DrugDiscovery #DrugDesign

[𝗪𝗼𝗿𝗸𝘀𝗵𝗼𝗽𝘀] Philly Area, Oct 9 - We’ll be conducting free hands-on drug design workshops at the Sheraton Valley Forge, King Of Prussia. The morning session will focus on Biologics: Protein Alignments, Modeling and Docking, while the afternoon will cover Small Molecule Docking and Fragment-based Design (see agenda below). This event is open to everyone, regardless of prior software experience. For course descriptions and to registration, please visit: https://bit.ly/3StDL7j AGENDA 09:00-12:00 𝗕𝗶𝗼𝗹𝗼𝗴𝗶𝗰𝘀: 𝗣𝗿𝗼𝘁𝗲𝗶𝗻 𝗔𝗹𝗶𝗴𝗻𝗺𝗲𝗻𝘁𝘀, 𝗠𝗼𝗱𝗲𝗹𝗶𝗻𝗴 𝗮𝗻𝗱 𝗗𝗼𝗰𝗸𝗶𝗻𝗴 This workshop covers essential methods for aligning protein sequences, superposing structures, loop modeling, building fusion protein models, and conducting protein-protein docking. Participants will learn techniques for grafting and refining antibody CDR loops, as well as using a knowledge-based approach to scFv fusion protein modeling with the Linker Modeler application. The session will also cover protein-protein docking of an antibody to an antigen and epitope mapping. Finally, the workshop will guide participants through a complete workflow for generating a QSAR model to predict and analyze protein/biologics solubility. 13:00-15:00 𝗦𝗺𝗮𝗹𝗹 𝗠𝗼𝗹𝗲𝗰𝘂𝗹𝗲 𝗗𝗼𝗰𝗸𝗶𝗻𝗴 This workshop will explore some variants of protein-ligand docking to predict the binding of small-molecule structures to a protein target. Pharmacophore-guided docking will be used to preserve key interactions, whereas template-based docking will efficiently position congeneric series of compounds in the binding site. Reaction-based covalent docking will generate poses for covalently bound ligands. Analysis of docking results and techniques to achieve high-throughput docking will also be addressed. 15:00-15:30 𝗕𝗿𝗲𝗮𝗸   15:30-17:00 𝗙𝗿𝗮𝗴𝗺𝗲𝗻𝘁-𝗕𝗮𝘀𝗲𝗱 𝗗𝗲𝘀𝗶𝗴𝗻: 𝗦𝗰𝗮𝗳𝗳𝗼𝗹𝗱 𝗛𝗼𝗽𝗽𝗶𝗻𝗴, 𝗙𝗿𝗮𝗴𝗺𝗲𝗻𝘁 𝗚𝗿𝗼𝘄𝗶𝗻𝗴 𝗮𝗻𝗱 𝗕𝗶𝗼𝗶𝘀𝗼𝘀𝘁𝗲𝗿𝗶𝗰 𝗥𝗲𝗽𝗹𝗮𝗰𝗲𝗺𝗲𝗻𝘁𝘀 This workshop will focus on applications for fragment-based drug design, covering methods such as scaffold hopping, fragment growing and R-group exploration to generate novel compound ideas, then optimize and score the structures in the pocket. The use of molecular descriptors and pharmacophore models to guide these computational methods will also be discussed. In addition, an SBDD method for generating closely related analogs through bioisosteric replacements will be presented. 17:00-18:00 𝗦𝗼𝗰𝗶𝗮𝗹 𝗛𝗼𝘂𝗿 - - - 𝗩𝗲𝗻𝘂𝗲: Sheraton Valley Forge 480 North Gulph Road, King Of Prussia, PA 19406 #DrugDesign #DrugDiscovery #CADD #SBDD #CompChem #MedChem #Biologics