Chemical Computing Group

[𝗔𝗡𝗡𝗢𝗨𝗡𝗖𝗘𝗠𝗘𝗡𝗧] Chemical Computing Group and the American Chemical Society’s Division of Computers in Chemistry (ACS COMP), congratulate the 𝗔𝗖𝗦 𝗙𝗮𝗹𝗹 2024 𝗖𝗖𝗚 𝗘𝘅𝗰𝗲𝗹𝗹𝗲𝗻𝗰𝗲 𝗔𝘄𝗮𝗿𝗱𝘀 𝘄𝗶𝗻𝗻𝗲𝗿𝘀! The CCG Excellence Awards have been created to stimulate graduate student participation in ACS COMP Division activities (symposia and poster sessions) at ACS National Meetings. Up to 10 awardees are chosen every year on the basis of the quality and significance of the research to be presented, as well as the strength of the supporting letter and other materials. Visit the ACS COMP Division Awards page for more information: http://bit.ly/2HyI1Nc 𝗧𝗵𝗲 𝗙𝗮𝗹𝗹 2024 𝗪𝗶𝗻𝗻𝗲𝗿𝘀 𝗠𝗼𝗻𝘁𝗴𝗼𝗺𝗲𝗿𝘆 𝗚𝗿𝗮𝘆; Ohio State University, Department of Chemistry and Biochemistry; John M. Herbert, mentor; “Using quantum mechanics to understand noncovalent interactions” 𝗗𝗮𝘃𝗶𝗱 𝗞𝗮𝘀𝘁𝗻𝗲𝗿; Massachusetts Institute of Technology, Department of Chemical Engineering; Heather Kulik, mentor; “Blueprints of C-H Bond Activation Across Iron-Containing High-Valent Metalloenzymes” 𝗝𝗼𝗿𝗱𝘆 𝗛𝗼𝗺𝗶𝗻𝗴 𝗟𝗮𝗺; University of Southern California, Department of Computational Biology and Bioinformatics; Vsevolod Katritch, mentor; “Anisotropic Vibrational Modes in Biomolecules with Millions of Atoms” 𝗫𝘂𝗲𝗻𝗮𝗻 𝗠𝗶; University of Illinois Urbana-Champaign, Center for Biophysics and Quantitative Biology; Diwakar Shukla, mentor; “Computational Characterization of Substrate Preferences of RiPP Biosynthetic Enzymes” 𝗘𝗿𝗻𝗲𝘀𝘁 𝗢𝗽𝗼𝗸𝘂; Auburn University, Department of Chemistry and Biochemistry; J. V. Ortiz, mentor; “Novel Electron-Propagator Methods for Computing Molecular Electron-Binding Energies and Dyson Orbital” #CompChem

Happy to share this recent publication coming out of our collaboration with Christian Kersten and Luca Peter Köhler.

We are excited to announce the final agenda for our North American drug design meeting, UGM & Conference 2024, Montreal. The general theme of our annual meeting is methods in early-stage drug discovery, ranging from computational/medicinal chemistry to topics in biologics. More information at https://bit.ly/3tVcArR >AGENDA< TUES., June 25  09:30 Parallel Drug Design Workshops WED., June 26  09:30 Parallel Drug Design Workshops 14:00 “Adventures in Large Chemical Space” - H. Purkey, Genentech 14:30 “Machine Learning Guided AQFEP...” - A. Bortolato, SandboxAQ 15:00 “Proteins, Partners, Pockets: Drug Discovery Exploration...” – S.F. Harris, Genentech 15:30 Break 16:00 “XForce: The Next Generation Force Field Parameter for All” - X. Hou, Pfizer 16:30 “Advancing Force Field Design and Development at Open Force Field” - L. Wang, Open Force Field Initiative 17:00 “AmberEHT Forcefield: Novel Approaches to Small Molecule Parameterization” - P. Labute, CCG 18:30 Opening Reception & Poster Session 21:00 Group Activities THUR., June 27  09:00 “From Water Structure to Pharmacophore Search” - D. McKay, Ventus Therapeutics 09:30 “The Art of Designing Out: Using Structure and Ligand Based Designing...” - A. Basu, Takeda 10:00 “MOE Deployment at Gilead & Unraveling of Cryptic Pockets” - Wilian Cortopassi, Gilead Sciences 10:30 Break 11:00 Historic Walking Tour 14:00 “Using Generative AI to Design Mini-Therapeutic Proteins Targeting a Heterodimeric Complex...” - L. Hammack, Merck 14:30 “Tuning and Validating Coarse-grained, Monte Carlo Simulations...” – J. Janke, Sanofi 15:00 “Antibody Sequence and Structure-Based Workflows for Diversity and Developability Assessments” - V. Kurella, Takeda 15:30 Break 16:00 “Dynamic Epitope Analysis of Antiviral mAbs” - K. Hauser, Vir Biotechnology, Inc. 16:30 “Computational Models to Predict and Guide Mitigation of Chemical Degradation in Antibodies” - S. Izadi, Genentech 17:00 “Method for Rapid Virtual Screening of Potential Antibody Binders” - S. Kumar, Moderna Inc. 18:30 Reception & Conference Dinner Cruise FRI., June 28  09:00 “Discovery of CNS Penetrant Indazole IRAK4 Inhibitors” - P. Bolduc, Biogen 09:30 “Beyond Ro5 Free Ligand Conformational and Dynamical Determinants of Passive Permeability...” - A. Balazs, AstraZeneca 10:00 “Understanding the Chameleonicity and Permeability of PROTACs...” – B. Taylor, Johnson & Johnson Innovative Medicine 15:30 Break 11:00 “Platform To Enable Structure-Enriched Models For Challenging Systems...”- U. Viswanathan, Janssen 11:30 “Discovery of Potent, Selective Type III RKIPK1 Inhibitors for the Treatment of Neurodegenerative Disease...” – Z. Brill, Merck 12:00 “25 Years of Drug Discovery (from Foundations to Drugs)” - J. Duca, Novartis 12:30 Closing Lunch > FEES < USD 475 > VENUE < Hotel Nelligan Montreal, Canada #DrugDiscovery #Biologics #MedChem #CompChem

We are excited to announce the final agenda for our North American drug design meeting, UGM & Conference 2024, Montreal. The general theme of our annual meeting is methods in early-stage drug discovery, ranging from computational/medicinal chemistry to topics in biologics. More information at https://bit.ly/3tVcArR >AGENDA< TUES., June 25  09:30 Parallel Drug Design Workshops WED., June 26  09:30 Parallel Drug Design Workshops 14:00 “Adventures in Large Chemical Space” - H. Purkey, Genentech 14:30 “Machine Learning Guided AQFEP...” - A. Bortolato, SandboxAQ 15:00 “Proteins, Partners, Pockets: Drug Discovery Exploration...” – S.F. Harris, Genentech 15:30 Break 16:00 “XForce: The Next Generation Force Field Parameter for All” - X. Hou, Pfizer 16:30 “Advancing Force Field Design and Development at Open Force Field” - L. Wang, Open Force Field Initiative 17:00 “AmberEHT Forcefield: Novel Approaches to Small Molecule Parameterization” - P. Labute, CCG 18:30 Opening Reception & Poster Session 21:00 Group Activities THUR., June 27  09:00 “From Water Structure to Pharmacophore Search” - D. McKay, Ventus Therapeutics 09:30 “The Art of Designing Out: Using Structure and Ligand Based Designing...” - A. Basu, Takeda 10:00 “MOE Deployment at Gilead & Unraveling of Cryptic Pockets” - Wilian Cortopassi, Gilead Sciences 10:30 Break 11:00 Historic Walking Tour 14:00 “Using Generative AI to Design Mini-Therapeutic Proteins Targeting a Heterodimeric Complex...” - L. Hammack, Merck 14:30 “Tuning and Validating Coarse-grained, Monte Carlo Simulations...” – J. Janke, Sanofi 15:00 “Antibody Sequence and Structure-Based Workflows for Diversity and Developability Assessments” - V. Kurella, Takeda 15:30 Break 16:00 “Dynamic Epitope Analysis of Antiviral mAbs” - K. Hauser, Vir Biotechnology, Inc. 16:30 “Computational Models to Predict and Guide Mitigation of Chemical Degradation in Antibodies” - S. Izadi, Genentech 17:00 “Method for Rapid Virtual Screening of Potential Antibody Binders” - S. Kumar, Moderna Inc. 18:30 Reception & Conference Dinner Cruise FRI., June 28  09:00 “Discovery of CNS Penetrant Indazole IRAK4 Inhibitors” - P. Bolduc, Biogen 09:30 “Beyond Ro5 Free Ligand Conformational and Dynamical Determinants of Passive Permeability...” - A. Balazs, AstraZeneca 10:00 “Understanding the Chameleonicity and Permeability of PROTACs...” – B. Taylor, Johnson & Johnson Innovative Medicine 15:30 Break 11:00 “Platform To Enable Structure-Enriched Models For Challenging Systems...”- U. Viswanathan, Janssen 11:30 “Discovery of Potent, Selective Type III RKIPK1 Inhibitors for the Treatment of Neurodegenerative Disease...” – Z. Brill, Merck 12:00 “25 Years of Drug Discovery (from Foundations to Drugs)” - J. Duca, Novartis 12:30 Closing Lunch > FEES < USD 475 > VENUE < Hotel Nelligan Montreal, Canada #DrugDiscovery #Biologics #MedChem #CompChem

We are excited to announce the final agenda for our North American drug design meeting, UGM & Conference 2024, Montreal. The general theme of our annual meeting is methods in early-stage drug discovery, ranging from computational/medicinal chemistry to topics in biologics. More information at https://bit.ly/3tVcArR >AGENDA< TUES., June 25  09:30 Parallel Drug Design Workshops WED., June 26  09:30 Parallel Drug Design Workshops 14:00 “Adventures in Large Chemical Space” - H. Purkey, Genentech 14:30 “Machine Learning Guided AQFEP...” - A. Bortolato, SandboxAQ 15:00 “Proteins, Partners, Pockets: Drug Discovery Exploration...” – S.F. Harris, Genentech 15:30 Break 16:00 “XForce: The Next Generation Force Field Parameter for All” - X. Hou, Pfizer 16:30 “Advancing Force Field Design and Development at Open Force Field” - L. Wang, Open Force Field Initiative 17:00 “AmberEHT Forcefield: Novel Approaches to Small Molecule Parameterization” - P. Labute, CCG 18:30 Opening Reception & Poster Session 21:00 Group Activities THUR., June 27  09:00 “From Water Structure to Pharmacophore Search” - D. McKay, Ventus Therapeutics 09:30 “The Art of Designing Out: Using Structure and Ligand Based Designing...” - A. Basu, Takeda 10:00 “MOE Deployment at Gilead & Unraveling of Cryptic Pockets” - Wilian Cortopassi, Gilead Sciences 10:30 Break 11:00 Historic Walking Tour 14:00 “Using Generative AI to Design Mini-Therapeutic Proteins Targeting a Heterodimeric Complex...” - L. Hammack, Merck 14:30 “Tuning and Validating Coarse-grained, Monte Carlo Simulations...” – J. Janke, Sanofi 15:00 “Antibody Sequence and Structure-Based Workflows for Diversity and Developability Assessments” - V. Kurella, Takeda 15:30 Break 16:00 “Dynamic Epitope Analysis of Antiviral mAbs” - K. Hauser, Vir Biotechnology, Inc. 16:30 “Computational Models to Predict and Guide Mitigation of Chemical Degradation in Antibodies” - S. Izadi, Genentech 17:00 “Method for Rapid Virtual Screening of Potential Antibody Binders” - S. Kumar, Moderna Inc. 18:30 Reception & Conference Dinner Cruise FRI., June 28  09:00 “Discovery of CNS Penetrant Indazole IRAK4 Inhibitors” - P. Bolduc, Biogen 09:30 “Beyond Ro5 Free Ligand Conformational and Dynamical Determinants of Passive Permeability...” - A. Balazs, AstraZeneca 10:00 “Understanding the Chameleonicity and Permeability of PROTACs...” – B. Taylor, Johnson & Johnson Innovative Medicine 15:30 Break 11:00 “Platform To Enable Structure-Enriched Models For Challenging Systems...”- U. Viswanathan, Janssen 11:30 “Discovery of Potent, Selective Type III RKIPK1 Inhibitors for the Treatment of Neurodegenerative Disease...” – Z. Brill, Merck 12:00 “25 Years of Drug Discovery (from Foundations to Drugs)” - J. Duca, Novartis 12:30 Closing Lunch > FEES < USD 475 > VENUE < Hotel Nelligan Montreal, Canada #DrugDiscovery #Biologics #MedChem #CompChem

[𝗖𝗢𝗡𝗙𝗘𝗥𝗘𝗡𝗖𝗘] We're looking forward to attending the PEGS Boston Summit next week in Boston (May 13-17). Check our posters and come visit us at booth # 823. For more information, please visit: https://bit.ly/3QG0Emp 𝗣𝗼𝘀𝘁𝗲𝗿 # B022: Exploring the Dynamic Changes of Nucleic Acids to Evaluate the Effect of Protonated Nucleotides on Structure and Binding In this work we use molecular modeling and molecular dynamics simulations to analyze the difference in structural and dynamic evolution between nucleic acids with protonated and unprotonated nucleotides. MD trajectories were post-processed using tools in the Molecular Operating Environment (MOE) to identify critical nucleic acid-specific dihedral angles, hydrogen bonds and contacts. 𝗣𝗼𝘀𝘁𝗲𝗿 # C022: 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 for those that are approved by the U.S. Food and Drug Administration (FDA). #Biologics #AntibodyModeling #ProteinEngineering #AntibodyTherapeutics

We will soon close registration (May 12) for our European UGM & Conference 2024, Lyon (see final program below). Scientific presentations are scheduled on May 23-24, hands-on drug design workshops on May 21-22. For more information, including abstracts, please visit https://bit.ly/45QhJPx > VENUE < Talks, Posters & Receptions: InterContinental Lyon - Hôtel Dieu Workshops: Hôtel Mercure Lyon Centre Lyon, France >AGENDA< TUES, May 21 - DAY 1 13:30 Workshops WED, May 22 - DAY 2 09:00 Workshops 18:30 Reception & Poster Session 20:45 Walking Tour THUR, May 23 - DAY 3 09:00 "Exploring Multiple Approaches for Predicting Permeability of Cyclic Peptides" | Claudia Beato, Evotec 09:30 "Cryo-EM Illuminates Modern Drug Discovery: Unveiling the Molecular Landscape Where Other Methods Fall Short" | Alexey Rak, Sanofi 10:00 "Design of Site-Specific Antibody-Drug Conjugates through Computational Modelling" | Elena de Orbe Izquierdo, AstraZeneca 11:00 "Predicting Post-Translational Modifications through Structural In Silico Analysis" | Elizabeth Rodriguez, UCB 11:30 "Towards Machine Learning Approaches for Predicting Chemical Liability" | Dilyana Dimova, Sanofi 12:00 "A Machine Learning Approach to Improving Antibody Developability" | Paul MacDonald, GSK 14:00 "Enhancing the Potency and Stability of TCR-based Therapeutics through in silico Engineering" | Tom Dixon, Etcembly Ltd. 14:30 "An all-inclusive package for ADMET and off-target Machine Learning" | Anke Hackl, Bayer Pharma AG 15:00 "Extending & Testing Poisson-Boltzmann Electrostatics with MOE" | Nicolas Foloppe, Vernalis 16:00 "The Open Force Field Initiative: An Update on Our Progress and Plans" | David Mobley, University of California, Irvine 16:30 "AmberEHT Forcefield: Novel Approaches to Small Molecule Parameterization" | Paul Labute, CCG 18:30 Conference Dinner Cruise FRID, May 24 - DAY 4 09:00 "Generative AI and Drug Design - Hallucinations and Reality" | Richard Cooper, Oxford Drug Design 09:30 "Quantum Chemistry Calculations of Nitrosamine Activation and Deactivation Pathways for Carcinogenicity Risk Assessment" | Andreas Göller, Bayer Pharma AG 10:00 "Deep Dive into Molecular Interactions: When Do They Translate into Measured in Vitro Binding/Activity?" | Anna Karawajczyk, Selvita S.A. 11:00 "Application of Absolute Binding Free Energy Calculations to Predict the Binding Modes and Affinities of Protein–Protein Inhibitors" | Léa El Khoury, Qubit Pharmaceuticals 11:30 “The Porphyrin Pathway” | Michael Charlton, MoA Technology Ltd 12:00 “Probing the Psychedelic Structure-Activity Space” | Chris Williams,CCG 14:00 “Biasing the Unbiased” | Didier Roche, Edelris 14:30 “The Role of QM/MM MD Simulations in Revealing the Complexity of hCHIT1 Enzyme, Its Mode of Action and Inhibition by OATD-01” | Mariusz Milewski, Molecure S.A. 15:00 “Fun with Functional Groups” | Peter Ertl, Novartis 15:40 Closing Reception > FEES < USD 475 (EUR ~450) #DrugDiscovery #Biologics #MedChem #CompChem

[This week 𝗹𝗶𝘃𝗲 𝘄𝗲𝗯𝗶𝗻𝗮𝗿] Thursday, May 2: X-Ray Crystallography: Structure Preparation, Electron Density and Solvent Analysis. In this webinar we will discuss methods for evaluating, analyzing and refining protein models derived from X -ray crystallographic data (see full description below). Anyone interested is welcome to attend. For more information and to register, please visit https://bit.ly/3Qo22de Webinar: X-Ray Crystallography: Structure Preparation, Electron Density and Solvent Analysis The webinar will cover methods for evaluating, analyzing and refining protein models derived from X-ray crystallographic data. Topics related to protein structure preparation and side-chain conformational analysis and placement will be discussed. Visualization and interpretation of electron density maps for assessing protein models will be described. The 3D-RISM method for predicting and refining the placement of solvent molecules in protein models will also be presented. #DrugDiscovery #CADD #DrugDesign #MedChem #CompChem #XRayCrystallography 

[This week 𝗹𝗶𝘃𝗲 𝘄𝗲𝗯𝗶𝗻𝗮𝗿] Thursday, May 2: X-Ray Crystallography: Structure Preparation, Electron Density and Solvent Analysis. In this webinar we will discuss methods for evaluating, analyzing and refining protein models derived from X -ray crystallographic data (see full description below). Anyone interested is welcome to attend. For more information and to register, please visit https://bit.ly/3Qo22de Webinar: X-Ray Crystallography: Structure Preparation, Electron Density and Solvent Analysis The webinar will cover methods for evaluating, analyzing and refining protein models derived from X-ray crystallographic data. Topics related to protein structure preparation and side-chain conformational analysis and placement will be discussed. Visualization and interpretation of electron density maps for assessing protein models will be described. The 3D-RISM method for predicting and refining the placement of solvent molecules in protein models will also be presented. #DrugDiscovery #CADD #DrugDesign #MedChem #CompChem #XRayCrystallography