CBB 399: The Role of NMR in Screening, Drug Discovery, and Lead Optimization

The Role of NMR in Screening, Drug Discovery, and Lead Optimization

The course will introduce the basics of Fragment-based Drug Discovery (FBDD) by NMR Spectroscopy with particular emphasis on detection and characterization of ligand binding to macromolecules. The course assumes no prior knowledge of NMR and will present the theoretical and practical aspects of various NMR techniques that are useful in FBDD as well as preparation of samples. Registered students will receive practical training in the analysis of NMR data from the above experiments and will acquire the knowledge needed to understand this novel method for discovering pharmaceuticals. An outline of the course is provided below:

Session 1: Introduction to the role of NMR in Drug Discovery
• NMR based fragment screening to identify binders to proteins and nucleic acids, especially “un-drugable targets”
• Hit validation to confirm if a small molecule/peptide identified from HTS binds to a target
• Identification of the binding site on the target protein
• Using fluorine NMR in fragment-based drug discovery
• NMR-based assays for determination of dissociation constants (affinity)
• Pharmacophore mapping to improve lead compounds

Session 2: Workshop on Fragment-based Drug Discovery
• Hands-on experience in analyzing complex data from an actual HMS ligand-detected screen
• Tutorial on using chemical shift perturbations to determine binding affinity
• Literature readings will be assigned prior to session 2 that will familiarize students with the techniques in the workshop
• Real-time demonstration of data acquisition using a model target/ligand system

Session 1 is open to all students, post-docs, faculty, and staff. Session 2 is only open to participants who register for the course through this website by Mon, May 1, 2017 at 9am EDT. Enrollment for day 2 is limited to 15 students (graduate students will be given priority over post-docs). Students who attend both days of the course and complete the assignment (see below) will be given course credit.

Questions regarding registration and enrollment in the course should be directed to Madhvi Venkatesh at madhvi_venkatesh@hms.harvard.edu.

Course Instructors:
• Hari Arthanari, PhD, Assistant Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Dana-Farber Cancer Institute
• Paul Coote, PhD, Research Associate in Biological Chemistry and Molecular Pharmacology, Harvard Medical School
• Gregory Heffron, Director, East Quad NMR Core Facility, Harvard Medical School

Curriculum Fellow: Madhvi Venkatesh
Course Director: Hari Arthanari

Schedule:
First Session: Thursday, May 4, 2017; 12:30PM - 5:00PM
Location: TMEC 227
Second Session: Thursday, May 11, 2017; 1:00PM - 4:00PM
Location: Countway L2-025

Class Assignment:
Enrolled students will be given a review article to read prior to the second session. The paper will be discussed at the beginning second session and students are expected to participate with their thoughts and questions about the paper.

AUDITORS (Post-Docs, Faculty, or Staff) DO NOT NEED TO SIGN UP TO ATTEND THE 1st SESSION. PLEASE DO NOT ENROLL.