The Spring 2008 Schrödinger User Symposium, June 4th-6th, showcased a variety of successful applications of Schrödinger software in drug discovery. Attendees were introduced to the diversity of methods in which computational chemists solve today's leading problems. The symposium also provided an opportunity for users to obtain an early look at the latest features within Schrödinger's Suite 2008. In addition to the scientific presentations, the User Symposium offered hands-on training and one-on-one discussions with Schrödinger's scientific staff.
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The symposium began with a half-day workshop on Desmond. Desmond is designed specifically for high-performance molecular dynamics simulations of biomolecular systems (see our Spring 2008 Newsletter for a detailed description). |
"[The] Desmond workshop was great. Extremely informative and beneficial." |
Presented research covered four broad and diverse areas: Protein Flexibility in Drug Discovery, Advanced Techniques in Lead Discovery, Virtual Screening, and Free Energy Approaches for Lead Optimization. The symposium featured presenters from around the globe representing industrial, academic, and governmental institutions, including: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Harvard Medical School, the NIH, Pfizer, and many more. Several presenters discussed recently published work, which is listed here.
The formal presentations opened Thursday morning with a thought-provoking chair-address by Dr. Michael Miller from Pfizer. Miller challenged attendees of the conference to consider the differences between potency and efficacy. He proposed that an understanding of ligand binding interactions within a receptor is not sufficient for designing marketable pharmaceutical drugs, but that new tools are needed to investigate and optimize the kinetics of ligand binding and release. Friday's session was chaired by Dr. Paul Lyne from AstraZeneca. Lyne introduced the variety of challenges facing virtual screening, and the rank-ordering and scoring of docked ligands.
Schrödinger's
Spring 2008 User Symposium included a variety of interesting topics
from a talented group of speakers (pictured above).
The symposium presentations included the successful application of Induced Fit Docking to predict a priori of any in vitro studies the variation in binding affinity of a potent inhibitor to multiple genotypes of the Hepatitis C Virus. Induced Fit Docking was also shown to be valuable in studies of Cytochrome P450, and G-Protein Coupled Receptor proteins. Multiple presenters utilized Prime homology models as their template for productive structure-based drug discovery. Several validation studies were presented confirming the accuracy of Prime's loop prediction and refinement, including studies of Src and Abl proteins. In addition, a head-to-head comparison of Prime against its leading competitors was presented, and Prime was found to be superior at loop prediction and side-chain refinement.
The
Spring 2008 User Symposium drew a large crowd of computational
scientists from pharmaceutical, commercial, governmental, and academic
institutions.
An overview of on-going efforts to identify an inhibitor for the Dengue virus via community efforts using GRID computing and Glide Virtual Screening were presented. Glide Virtual Screening was tested in a docking validation study of antiviral targets in which Glide was found to outperform ICM. Pharmacophore modeling with Phase was shown to delineate structural features pertinent for potent GABAc receptor antagonism. CombiGlide Core Hopping was shown to be a useful tool for lead discovery of antibiotic resistant TGase.
The presentations concluded Friday with multiple studies of free energy approaches, including Prime MM-GBSA, linear interaction approximation (LIA) with Liaison, and free energy perturbations (FEP) with MCPRO. Multiple computational models were examined, and Prime MM-GBSA was shown as an advantageous alternative to FEP given its comparable accuracy and much higher computational efficiency. Furthermore, the easy configurability of Schrödinger KNIME Extensions was demonstrated by a practical workflow to compare free energies computed for CombiGlide-generated structures using both Prime MM-GBSA and Liaison.
The
closing reception was hosted at Schrödinger's Portland office, which
provided an engaging environment for further scientific discussion.
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"A large amount of time was available for networking and discussing methodology and basic science. The venues for the networking sessions were great and really fostered a good environment for exchange." |
The symposium was held at the historic Benson Hotel in downtown Portland, Oregon with the closing reception on Friday evening at Schrödinger's Portland office. Besides the closing reception, there were ample networking opportunities throughout the symposium, including the Thursday evening sessions, which provided opportunities for attendees to work directly with Schrödinger's technical staff. |