Davidson D001x – Medicinal Chemistry – The Molecular Basis of Drug Discovery

Instructor – Erland Stevens – Davidson College

Start Date – Monday, 02 October 2017

I. Learning Objectives

The overall goal of this course is to teach a student how to relate the chemical structure of a
drug to its biological function. An outcome of this goal is that a student who completes this
course will be able to attend lectures on drug discovery and reasonably understand the content
of the lectures.

• Recall the major steps of drug development and their corresponding processes
• Interpret relationships between molecule concentration and enzyme or receptor activity
• Compute a molecule's pharmacokinetic parameters from Cp-time data points
• Correlate a molecule's structure to its metabolic behavior
• Prioritize the viability of weakly active molecules for potential drug development
• Propose molecules with improved properties based upon data from related structures

II. Prerequisites

Students should be able to be able to identify organic chemistry functional groups and read
line-angle chemical structures. Students should also know the parts of a cell and be
comfortable working with mathematical expressions containing exponents and logarithms.
Students who lack the necessary organic chemistry experience may be able to supplement their
knowledge through lectures offered by Khan Academy.

III. Required Materials

This course does not have a required textbook. All materials for the course will be provided
through the edX platform. Students have access to a spreadsheet application. Examples
include Microsoft Excel, Apache OpenOffice, and LibreOffice (free, downloadable office suite
programs), and Google Docs Spreadsheet (available to anyone with a free Google account). The
spreadsheet application will allow analysis of data that will be encountered throughout the
course. The MOOC includes instructions on how to complete tasks with Google Docs
Spreadsheet. The instructions should also be helpful for the use of other spreadsheet
applications.

Past students in the course have recommended Web 2.0 calc as a convenient online calculator.
Many students in MOOCs download the video content of the course. A free video player that is
highly recommended by previous students is VLC.

IV. Registration

Students can register for the course under two different categories: honor code and ID verified.
Honor code students take the course for free. The ID verified track costs $50 and requires
students to confirm their identity as they log into the course. Students who intend to use this
course as a professional credential may want to consider registering in the ID verified category.
Students may sample the entire course before switching to ID verified status. The deadline for
registering for the ID verified track is Friday, 24 November 2017. Students who do register
under the ID verified track are encouraged to immediately confirm their enrollment status on
their edX dashboard page.

Students who are registered under the ID verified track will receive a certificate of completion if
they pass the course with an overall grade of at least 70%. Although a students may achieve a
passing grade before all of the content has been released, no certificates will be issued until
after the final grading deadline on Monday, 04 December 2017. The target date for issuance of
certificates is Friday, 08 December 2017.

V. Course Schedule - course launch Monday, 02 October 2017 at 15:00 UTC

Course content will be released on a weekly basis. All course assignments will remain open for
grading until the final deadline of the course (Monday, 04 December 2017 at 15:00 UTC). There
is a 24-h grace period for all assignments, including the final deadline.

Week 1 – release date Monday, 02 October 2017 at 15:00 UTC

Chapter 1 – Pre-Regulatory Medicine
Chapter 2 – Drug Discovery: From Concept to Marketplace
Week 1 Expert Interview – Natalie Clayton, Partner, Alston & Bird
Week 1 Virtual Lab – Designing molecules with potency

Week 2 – release date Monday, 09 October 2017 at 15:00 UTC

Chapter 3 – Proteins
Chapter 4 – Enzymes
Chapter 5 – Receptors
Week 2 Expert Interview - Dr. Steven Tregay, CEO, FORMA Therapeutics
Week 2 Virtual Lab - FoldIt - a protein modeling program
*** Examination 1 ***

Week 3 – release date Monday, 16 October 2017 at 15:00 UTC

Chapter 6 – Blood and Drug Transport
Chapter 7 – Pharmacokinetics
Week 3 Expert Interview – Dr. Parisa Zamiri, Director of Translational Medicine at
Novartis
Week 3 Virtual Lab – Designing molecules with potency and selectivity

Week 4 – release date Monday, 23 October 2017 at 15:00 UTC

Chapter 7 – Pharmacokinetics (con't)
Chapter 8 – Metabolism
Week 4 Expert Interview – Dr. James Mangold, Director of DMPK at Novartis
Week 4 Virtual Lab – Designing molecules with multiple optimized properties
 *** Examination 2 ***

Week 5 – release date Monday, 30 October 2017 at 15:00 UTC

Chapter 9 – Structure and Diversity
Week 5 Expert Interview – Dr. Adam Hill, Head of Screening at Novartis
Week 5 Virtual Lab – Designing Ibuprofen Analogues with SeeSAR

Week 6 – release date Monday, 06 November 2017 at 15:00 UTC

Chapter 10 – Lead Discovery
Week 6 Expert Interview – Dr. Meir Glick, Head of in silico Lead Discovery at Novartis
Week 6 Virtual Lab – Designing Histamine Ligands that Do Not Cross the BBB with
SeeSAR

Week 7 – release date Monday, 13 November 2017 at 15:00 UTC

Chapter 11 – Lead Optimization
Week 7 Expert Interview – Dr. Julien Levell, Group Leader in Global Drug Discovery at
Novartis
Week 7 Expert Interview – Dr. Amin Kamel, Senior Research Investigator II at Novartis
Week 7 Expert Interview – Dr. Parisa Zamiri, Director, Translational Medicine Expert at
Novartis
Week 7 Virtual Lab – Designing an Orally-Available Protease Inhibitor with SeeSAR
*** Examination 3 ***

Final deadline for all graded content - Monday, 04 December 2017 at 15:00 UTC

VI. Grading

The course grade is based on four types of assignments: in-chapter exercises (ICE),
examinations (EX), class participation (CP), chats (CH) and extra credit (EC). The passing grade
for this course is 70%. Grades on individual assignments can be below 70%, but the student's
overall grade must be at least 70%.

• in-chapter exercises (ICE) – These assignments are found in almost each subsection of
the course. In general, almost every lecture video will have at least one ICE associated
with it. Students may work with others on the ICEs, and questions to the discussion
board on the ICEs is permitted and even encouraged. The ICEs account for 60% of the
total course grade.
• examinations (EX) – The three exams are found at the end of Weeks 2, 4, and 7.
Students must work independently on the exams, although they are free to use all the
resources provided in the course to answer the questions (i.e., open-book and open-
note exam). The exams account for 30% of the total course grade.
 • class participation (CP) - Students receive class participation credit by working on the
Virtual Labs and watching the expert interviews. The class participation score counts for
10% of the total course grade.
• extra credit (EC) - Extra credit is available to students for completing surveys at the start
and finish of the course as well as completing the pre- and post-test. Students may add
up to 5% of the total possible points through extra credit (i.e., maximum course grade =
105%).

A comment on the grading of questions

All grade scores assigned within the course are final once a student submits an answer. Given
the online format of the course and the fact that enrollment will include thousands of students,
individual grade adjustments are not feasible. The staff of D001x acknowledges the possibility
that some questions in the course may not be ideally worded or the correct answer may be
somewhat subjective. The inclusion of extra credit points is intended to offset any instances of
poorly worded questions.

VII. Honor Code

In order to participate in this or any other edX course, a student must agree to abide by the edX
Honor Code Pledge (scroll down within the linked page). Under the terms of the pledge,
students may collaborate on the questions and exercises in each chapter. The examinations,
however, must be completed independently by each student.

VIII. Discussion Board

The course has a discussion board for interaction between students, course teaching assistants,
the instructor, and technical support staff. Students are encouraged to participate on the
discussion board for assistance with course material and to converse with other students on
related topics. Students may discuss course content, but any posts that disclose answers to
an assessment question will be edited or deleted by the course staff. Students are expected
to follow the guidelines below, which are taken from the World Wide Web Consortium (W3C)
web site. The edX Terms of Service provide similar guidelines for behavior of all edX
participants.

• Tone of messages must be maintained at the highest level of professionalism; flaming,

sarcasm, or personal attacks will not be tolerated.
• Don't attack a person. Disagree with an idea.
• Respect the right of others to disagree.
• Be polite and show respect. If you have nothing new, positive, informative or helpful to
say, refrain from sharing it.
• It's inappropriate to repeat the same argument over and over without adding new
information.
 • Debate; Don't argue.
• Listen; Don't shout.
• Stay on topic.

Students who fail to adhere to these guidelines will experience one of more of the following
consequences.

• Private warning
• Public warning
• Voluntary time out
• Involuntary time out
• Permanent removal from the discussion board

IX. Hints and Tips

• Print the materials for the course

Each video clip has an available summary. Print and read the video summaries for
additional insight into the course material.
• Take notes on both the video and written content of the course
Record your own notes on the printed materials so that you can make connections
between the topics.
• Use the discussion board
There is no reason to be confused or frustrated. Reach out to your fellow students and
the course staff through the discussion board. The board is actively monitored
throughout the day.
• Protect your time
When working on the course, minimize your distractions, and be prepared to focus on
the material. The more time you put into the course, the more you will receive from it.