Structural Biology and Computational Biophysics

Module and discussion leaders:
Yessica Gomez
Daniel Asarnow
Ilan Chemmama
Kyle Lopez
Andrew Natale
Sophia Tan

Grabe Lab
Cheng Lab
Sali Lab
Southworth Lab
Grabe Lab
DeGrado Lab

Structural biology provides a physical basis for our understanding of biological molecules, and allows us to rationalize how perturbations such as drug binding or heritable mutations alter a molecule's function. Nonetheless, the minuscule size of these machines, and their inherent flexibility, make this a challenging endeavor. To dig into this challenge, we will introduce experimental methods for probing macromolecular structures. Then, we will examine how computational approaches can inform models derived from experimental data, allowing us to characterize both the static and dynamic properties of a molecule. Finally, we can use this knowledge in our efforts to engineer proteins, to develop or repurpose pharmaceutical drugs, and to gain insight into the molecular mechanism of human disease.

  1. Develop an understanding of the power and limitations of structural and computational techniques to inform biological function.
  2. Gain hands-on experience with structural and computational modelling.
  3. Become familiar with current research in structural and computational biology at UCSF, and explore possibilities for rotation labs.


September 10th, 2018



9:00AM - 9:10

Arrive + coffee
9:10 - 9:30 Introduction to Structural Bio bootcamp
 9:30 - 10:30 Experimental methods in Structural Bio
 10:30 - 10:45 Break
 10:45 - 12:00PM Small group paper discussions
 12:00 - 1:00 Lunch + prepare journal club presentations
 1:00 - 2:00 Group journal club presentations
 2:00 - 3:00 Computational biophysics
 3:00 - 4+ Molecular dynamics programming activity

Paper Discussions:
We will break up into small groups for paper discussions, with each group discussing one of the papers below. Then we will reconvene and each group will briefly summarize their paper and the key points from their discussion for the class.

Paper Groups:

1) Elizabeth, Stephanie, Maria
Integrative structure and functional anatomy of a nuclear pore complex
Nature 555475482 (2018)

2) Laurel, Daniel, Ajikarunia
Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser
Science 361 (2018)

3) Garrett, Maurisa, Hayarpi
Electron cryomicroscopy observation of rotational states in a eukaryotic V-ATPase
Nature 521241245 (2015)

4) Christina, Elissa, Calla
Atomistic insight into lipid translocation by a TMEM16 scramblase
PNAS 113 (49), 14049-14054 (2016)

5) Matthew, Miraim, Bryan
Structural basis for nucleotide exchange in heterotrimeric G proteins
Science 348, 1361-1365 (2015)

6) Nicholas, Jack, Laura
Computational design of orthogonal membrane receptor-effector switches for rewiring signaling pathways
PNAS 115 (27), 7051-7056 (2018)

Activities (Files & Instructions):

Molecular Dynamics Activity

Research in Structural & Computational Biology at UCSF:
UCSF has a strong history in the fields of structural and computational biology, with many labs continuing that tradition today. Highlights include development of the DOCK program for drug design, creation of the AMBER force field for molecular dynamics simulations, decades of pioneering efforts in X-ray crystallography, and key developments leading to the "resolution revolution" in cryo-EM. Additionally, visualization of molecular structures is also a strength at UCSF. ChimeraX is actively developed here, and PyMOL was initially created by a UCSF alum.

At UCSF you will have a vast array of resources at hand, here are some highlights:

Macromolecular Structure Group  – facilities for X-ray crystallography, Cryo-EM, and SAXS
 UCSF NMR Lab  – facilities for NMR
 Resource for Biocomputing, Visualization, and Informatics  – Chimera, Integrative Modeling, etc
 Small Molecule Discovery Center  – high throughput screening to find leads for drug discovery
 Nikon Imaging Center at UCSF  – light microscopy facilities
 Center for Advanced Technology  – sequencing, cytometry, and much more

Many labs at UCSF conduct research in structural biology and computational biophysics:

 David Agard  – Structural basis for biological function of Hsp90 and tubulin polymerization
 Michelle Arkin
 – Small molecule drug discovery
 Patricia Babbitt
 – Computational methods for rational protein design
 Yifan Cheng  – Cryo-EM on TRP channels, ABC transporters, and the proteasome
 Seemay Chou  – Mechanism of surface recognition in host-pathogen interactions
 Charles Craik  – Infectious disease and cancer; antibody and small molecule therapeutics and diagnostics
 Bill DeGrado  – Molecular design as an approach to understanding macromolecular structure and function
 Shawn Douglas  – Design of DNA nanostructures
 Pamela England  – Ion channel structure‐function
 Tom Ferrin  Molecular graphics and visualization; structure-based drug design
 Alan Frankel  – RNA‐protein complexes; HIV
 James Fraser  Conformational heterogeneity in proteins
 Adam Frost  Structures and functions of cellular machines
 Michael Grabe  Computational methods for understanding ion channels and transporter function
 John Gross  – Structural & biochemical investigation of RNA dynamics and HIV-host protein complexes
 Bo Huang  – Super-resolution light microscopy to investigate genome architecture & subcellular compartments
 Matt Jacobson  Physics-based methods for modeling proteins and protein-ligand complexes
 Lily Jan  – Structure‐function of potassium channels in heart and hippocampus
 Natalia Jura  – Structure-function studies of EGFR, HER3, and the non-catalytic function of protein kinases
 Tanja Kortemme  Prediction and design of protein interactions; synthetic biology
 Sue Miller  Enzyme mechanisms
 Daniel Minor  – Structure and function of ion-channels
 Geeta Narlikar  – Chromatin remodeling
 Oren Rosenberg  – Structure and function of bacterial pathogenesis
 Andrej Sali  Modeling of protein structures and molecular assemblies
 Brian Shoichet  Computational chemistry; structure-based drug design
 Kevan Shokat  – Chemical tools for studying cellular signaling cascades; protein engineering
 Robert Stroud  – X-ray crystallography of membrane proteins
 Ron Vale  – Microtubule‐based motor proteins
 Peter Walter  – Protein sorting and organelle biogenesis
 Jim Wells  – Small molecule drug discovery

General Resources:

 UCSF Macro Website
 Resources page from Macromolecular Interactions course; a lot of useful material!
 RCSB Protein Data Bank (PDB)  Main resource for structural models (crystallography, NMR, EM, SAXS)
 EM Data Bank (EMDB)  Database for electron microscopy density maps
 SBGrid Data Bank  Database for raw diffraction frames