Biophysics 204B: Methods in Macromolecular Structure

Winter 2026 Syllabus

What is the next experiment?

Course Title: Methods in Macromolecular Structure

Course Format: 4 hours of lecture/group work per week in class, substantial group work outside of class hours

Location and Date/Hours: Tuesday, 9:00-10:30AM , Thursday 9AM-11:30AM in Genentech Hall 227

Prerequisites: All incoming first-year BP graduate students are required to enroll in this course.

Grading: Letter grade

Textbook: None. Lab protocols and course materials will be available in class or online

Instructors: John Gross, Tom Goddard, Dan Southworth

TAs:

Lecturers/Facilitators:

John Gross, Tom Goddard, Dan Southworth

Background:

Fluency in multiple biophysical methods is often critical for answering mechanistic questions. Traditionally, students are exposed to the fundamentals of multiple techniques through lectures that cover the theory before exposure, and, for some, in analysis or data collection during lab rotations. However, this structure means that only students who rotate in specific labs gain hands-on exposure, which could limit adventurous experiments in future years. To train the next generation of biophysicists at UCSF, we have decided to alter this traditional structure by creating “Macromolecular Methods”, a class that places emphasis on playing with data. We have designed Macromolecular Methods to be a team-based class where students develop their own analysis of real data that, in non-pandemic years, they have collected. The goal of this course is to provide students with sufficient exposure to major methods in biophysics to enable them to pursue these more fully in their independent research.

Course Description:

This is a team-based class where students work in small groups to develop their own analysis of real data. Statistical aspects of rigor and reproducibility in structural biology will be emphasized throughout lectures, journal club presentations, and hands-on activities. The website for the 2017, 2018, 2019, 2020 editions are available online.

Course expectations: This course will likely be different from most other courses you have taken before. Our expectation is that you will maximize your learning by being an active participant - there is significant out-of-class work required to enable this. Many learning opportunities will arise if you are willing to take advantage of the hands-on experience and from those who take the time to show you interesting aspects of the various methods. Data analysis will not follow a linear path - our expectation is that you start to become comfortable with unknowns and messy results. It is likely that you will encounter issues using the various scientific software required for the course - while we will help troubleshoot, navigating these challenges effectively is a core expectation that we want to see students build towards during the course.

Ethics: This course is more than a training experience; data analysis is part of ongoing active research projects, the results of which will be published to the broader scientific community. The community must be able to understand our work, replicate it, and have confidence in its findings. We must therefore ensure the integrity of the information we disseminate. To do so, it is essential that students perform and document their experiments and analyses as faithfully as possible. Mistakes and oversights are normal and to be expected, but they must not be ignored, concealed, or disguised.

Respect: This course is built around an open research project performed in teams. Successful completion of the course objectives will require that students work together effectively, so please respect the time and effort of your classmates and instructors. Moreover, as part of the research process, we will consider and debate a variety of ideas and approaches; however, we must not allow our position on a particular idea or argument to compromise our respect for its author. We therefore expect course participants to give all instructors and students, regardless of academic or personal background, their complete professional respect; anything less will not be tolerated.

Accommodations for students with disabilities: The Graduate Division embraces all students, including students with documented disabilities. UCSF is committed to providing all students equal access to all of its programs, services, and activities. Student Disability Services (SDS) is the campus office that works with students who have disabilities to determine and coordinate reasonable accommodations. Students who have, or think they may have, a disability are invited to contact SDS (StudentDisability@ucsf.edu); or 415-476-6595) for a confidential discussion and to review the process for requesting accommodations in classroom and clinical settings. More information is available online at http://sds.ucsf.edu. Accommodations are never retroactive; therefore students are encouraged to register with Student Disability Services (http://sds.ucsf.edu/) as soon as they begin their programs. UCSF encourages students to engage in support seeking behavior via all of the resources available through Student Life, for consistent support and access to their programs.

Commitment to Diversity, Equity and Inclusion: The course instructors and teaching assistants value the contributions, ideas and perspectives of all students. It is our intent that students from diverse backgrounds be well-served by this course, that students’ learning needs be addressed both in and out of class, and that the diversity that the students bring to this class be viewed as a resource, strength and benefit. It is our intent to present materials and activities that are respectful of diversity: gender identity, sexuality, disability, age, socioeconomic status, ethnicity, race, nationality, religion, and culture. However, we also acknowledge that many of the literature examples used in this course were authored in an environment that marginalized many groups. Integrating a diverse set of experiences is important for a more comprehensive understanding of science and we strive towards that goal. Although the instructors are committed to continuous improvement of our practices and our learning environment, we value input from students and your suggestions are encouraged and appreciated. Please let the course director or program leadership know ways to improve the effectiveness of the course for you personally, or for other students or student groups.

2026 schedule

TEAM ASSIGNMENTS

Team name: 1

Team name: 2

Team name: 3

JOURNAL CLUB ASSIGNMENTS

Link

Tuesday, January 6

9:00-10:30AM Introduction to the Course and Software Check

Jan 8-20 Structure Prediction and Drug Interaction Prospecting with AF3 (Tom Goddard)

Thursday January 8

9:00-11:30AM Visualizing and comparing atomic models with ChimeraX

Tuesday January 13

9:00-10:30AM Predicting ligand binding using AlphaFold 3 on the UCSF Wynton Cluster (Tom Goddard)

Additional links

Thursday January 15

Group Work, Ligand Screening with AF3

Tuesday January 20,

Group Presentations, 20 minutes + 10 min Q&A

Jan 22- Feb 12 Electron Microscopy (Dan Southworth), Practicals Max Tucker, Alex Long, Greg Merz, Eric Tse and Arthur Melo

Thursday, January 22

Cryo-EM Sample Preparation (note special classrooms)

Tuesday, January 27

Cryo-EM Data Collection

Thursday, January 29

Particle picking/2D Classification

Tuesday, February 3

Analyses of 3D classes and refinement

Thursday, February 5

Fitting and 3D refinement

Tuesday, February 10

Model Building

Thursday, Feb 12 Final presentations 20 minutes + 10 Q&A

Supplemental material and tutorial videos

Feb 17-March 10 Protein NMR , Nanobodies for SARS-CoV-2 Spike- John Gross, Dominic Grisingher and Catherine Kuhn

Tuesday, Feb 17th, The Fourier Transform and NMR Data processing

Thursday, Feb 19th, Process 15N HSQC of nanobody and nanobody Spike complexes

Tuesday, Feb 24th Hands-on Data collection (Dominic Grisingher and Catherine Kuhn)

9:00-11:30AM Acquiring and processing 15N HSQC Data

Note special location: groups will meet in NMRLAB GH S106 for data acquisition or Mission Hall 2105 for processing

Thursday Feb 26th

Introduction to ILV labeling of proteins for methyl group NMR

Tuesday, Mar 3rd

Chemical shift perturbation (CSP) mapping

Thursday, Mar 5th, class meets in GH-S261

Materials for TA Office Hours

Tuesday, March 10

Final Presentations NMR, 20 minutes + 10 min Q&A

Reading on rigor and reproducibility in NMR: