Channel Title: Molecular Memory Channel Description: Welcome! I'm KP, and I'm an organic chemist that loves making videos and sharing free chemistry and biochemistry resources. I hope you enjoy and learn something! <video> PyMOL 101, Lesson 5: Select by Distance, the Mouse Control Menu, and Labeling Description: In this lesson, KP will show you how to generate a binding site quickly, by creating a selection sphere within a certain number of angstroms from a bound ligand. This lesson focuses on the mouse control menu, and how to use edit mode to reposition labels. 00:00 Intro 00:26 Setting up your workspace 01:57 The mouse control menu 02:34 Selected by distance from a ligand 03:41 Adjusting water sphere size 04:09 Find polar contacts (display binding site interactions) 04:46 Modifying the binding site residue selection 05:50 Show only the amino acid side chains 06:25 Labeling the binding site residues 06:44 Edit mode and moving labels 07:41 Display the binding site without cartoon REFERENCES • PDB ID: 6PFK • Schirmer, T., Evans, P. Structural basis of the allosteric behaviour of phosphofructokinase. Nature 343, 140–145 (1990). https://doi.org/10.1038/343140a0 </video> <video> PyMOL 101, Lesson 1: GUI Basics - loading structures, mouse/trackpad motions, sequence, zoom & clip Description: In this first installment of PyMOL 101, KP teaches you the basics of the PyMOL Graphical User Interface (GUI, pronounced “gooey”). In lesson 1, you’ll learn to: • Load the biological unit of structures • Rotate, zoom, and reposition molecules • Interpret the sequence display • Zoom in on a feature of a particular structure • Adjust clipping CHAPTERS 00:00 - Intro 00:38 - Loading Structures 02:37 - Takeaways from Loading Structures 02:58 - Mouse/trackpad controls 04:10 - Sequence 05:26 - Zooming and Clipping REFERENCES: • The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC. (Video made with Version 2.4.2) • Berman, Helen M., et al. "The protein data bank." Nucleic acids research 28.1 (2000): 235-242. • The Protein Databank Website https://www.rcsb.org/ • PDB ID: 4mqk (Carbonmonoxy Structure of the Human Fetal Hemoglobin Mutant HbF Toms River alphawtgammaV67M) </video> <video> PyMOL: Superimpose (& Amazing NMR Structures!) Description: How to superimpose proteins to examine structural changes, and a look at how we can explore protein dynamics with NMR solution structures. </video> <video> PyMOL Tutorial: Modeling the SARS-CoV-2 RBD Interactions with ACE (COVID-19 Coronavirus Proteins) Description: A follow up PyMOL tutorial for my SARS-CoV-2 Structure. How I modeled the polar interactions between the spike protein RBD and ACE before the paper was published (and a follow up interaction now that the paper is published!) PDB ID: 6VW1 Reference: Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., ... & Li, F. (2020). Structural basis of receptor recognition by SARS-CoV-2. Nature, 1-8. </video> <video> SARS-CoV-2 Structure (COVID-19 Coronavirus) Description: A structural exploration of the proteins produced by SARS-CoV-2. PDB FILES: 6VSB - Spike protein 6VW1 - RBD of the spike protein in complex with ACE2 6SGC - Rabbit ribosome stalled on a poly-A tail 6Y2E - SARS CoV-2 main protease 6Y2F - SARS CoV-2 main protease bound to an inhibitor REFERENCES: • Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C. L., Abiona, O., ... & McLellan, J. S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 367(6483), 1260-1263. • White, J. M., Delos, S. E., Brecher, M., & Schornberg, K. (2008). Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. Critical reviews in biochemistry and molecular biology, 43(3), 189-219. • Zhang, L., Lin, D., Sun, X., Curth, U., Drosten, C., Sauerhering, L., ... & Hilgenfeld, R. (2020). Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. • Fehr, A. R., & Perlman, S. (2015). Coronaviruses: an overview of their replication and pathogenesis. In Coronaviruses (pp. 1-23). Humana Press, New York, NY. </video> <video> Understanding PHI and PSI Angles, Ramachandran Plots, & Newman Projections Description: This video was created using models, images, and inspiration from the Proteopedia page: The Ramachandran Principle Phi (φ) and Psi (ψ) Angles in Proteins https://proteopedia.org/wiki/index.php/Tutorial:Ramachandran_principle_and_phi_psi_angles REFERENCES: • Ramachandran, G.N.; Ramakrishnan, C.; Sasisekharan, V. (1963). "Stereochemistry of polypeptide chain configurations". Journal of Molecular Biology. 7: 95–9. • Prilusky J, Hodis E, Canner D, Decatur W, Oberholser K, Martz E, Berchanski A, Harel M, Sussman JL. Proteopedia: A status report on the collaborative, 3D web-encyclopedia of proteins and other biomolecules. J Struct Biol. 2011 Apr 23. PMID:21536137 doi:10.1016/j.jsb.2011.04.011 </video> <video> Antibody Structure: The Immunoglobulin Fold and Antibody-Antigen Interactions Description: Dr. KP gives an overview of antibody structure, and takes a look at a human antibody bound to the SARS-CoV-2 spike protein. PDB IDs Available at rcsb.org: 1igt, 7k90 REFERENCES • Akkaya, M., Kwak, K. & Pierce, S.K. B cell memory: building two walls of protection against pathogens. Nat Rev Immunol 20, 229–238 (2020). https://doi.org/10.1038/s41577-019-0244-2 • Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. • Barnes, C.O., Jette, C.A., Abernathy, M.E. et al. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature 588, 682–687 (2020). https://doi.org/10.1038/s41586-020-2852-1 • Chiu ML, Goulet DR, Teplyakov A, Gilliland GL. Antibody Structure and Function: The Basis for Engineering Therapeutics. Antibodies (Basel). 2019;8(4):55. Published 2019 Dec 3. doi:10.3390/antib8040055 • Lambert, J. M., & Berkenblit, A. (2018). Antibody–drug conjugates for cancer treatment. Annual review of medicine, 69, 191-207. • Nose M, Wigzell H. Biological significance of carbohydrate chains on monoclonal antibodies. Proc Natl Acad Sci U S A. 1983;80(21):6632-6636. doi:10.1073/pnas.80.21.6632 • Pan S, Manabe N, Yamaguchi Y. 3D Structures of IgA, IgM, and Components. Int J Mol Sci. 2021;22(23):12776. Published 2021 Nov 26. doi:10.3390/ijms222312776 • Vollmers, H. Peter, and Stephanie Brändlein. Natural antibodies and cancer. New biotechnology 25.5 (2009): 294-298. </video> <video> Where's My Dimer? Symmetry Mates in PyMOL Description: If you've ever modeled a protein in PyMOL and it looks like you're missing a subunit of your dimer, you may need to generate a symmetry mate to visualize the whole structure. This tutorial will help! </video> <video> PyMOL 101 Lesson 2: Basic Selection, Show, Hide, and Actions Menus (Carbonic Anhydrase Active Site) Description: In this lesson, KP demonstrates how to display the active site of carbonic anhydrase using the active site amino acid information from a manuscript. We’ll learn how to save and change the renderings of selections in the names panel. Then, we’ll use our selections to identify water molecules that are hydrogen bonding to the active site. Don’t forget to save your work at the end of this lesson—we’ll use the PyMOL file in Lesson 3! 00:00 Introduction and carbonic anhydrase 00:40 Setting up your workspace 01:00 Finding the journal article from the PDB page 01:18 Terminology break 01:42 Saving selections 02:45 Selecting active site residues 05:06 Renderings and Show/Hide Buttons 06:53 Locate and display active site water 08:17 Show/Hide amino acid backbone (main chain) REFERENCES • The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC. • Dutta, S. and Goodsell, D. 2004. Molecule of the Month: Carbonic Anhydrase http://doi.org/10.2210/rcsb_pdb/mom_2004_1 • PDB ID: 3uyn • Elder, I., Fisher, Z., Laipis, P. J., Tu, C., McKenna, R., & Silverman, D. N. (2007). Structural and kinetic analysis of proton shuttle residues in the active site of human carbonic anhydrase III. PROTEINS: Structure, Function, and Bioinformatics, 68(1), 337-343. </video> <video> PyMOL 101, Lesson 4: Color, Transparency, and Alternate Renderings Description: In this installment of PyMOL 101, KP talks about CPK coloring and color settings in PyMOL. We’ll learn to change renderings, color them, and apply transparency. 00:00 Intro AND CPK coloring 00:40 Phosphofructokinase background 01:24 Setting up your workspace 02:06 Color by chain 03:23 Color by secondary structure 03:52 Surface transparency 04:51 Color by element 06:05 Terminology break 06:28 Rendering a ligand 07:26 Cartoon transparency 08:14 Overview of the different renderings REFERENCES: • https://proteopedia.org/wiki/index.php/CPK#:~:text=CPK%20Color%20Scheme%20for%20the,yellow%2C%20and%20hydrogen%20is%20white. • PDB ID: 6PFK • Schirmer, T., Evans, P. Structural basis of the allosteric behaviour of phosphofructokinase. Nature 343, 140–145 (1990). https://doi.org/10.1038/343140a0 </video> <video> The Mechanisms of Glycolysis (Part 2) Description: Dr. KP takes you through the arrow pushing for the final 5 steps of glycolysis. These reactions are part of the energy-yielding payoff phase of the pathway! 00:00 Intro 00:24 Glyceraldehyde-3-phosphate dehydrogenase 04:47 Phosphoglycerate kinase 05:46 Phosphoglycerate mutase 07:14 Enolase 08:45 Pyruvate kinase REFERENCES: • Appling, D. R., Anthony-Cahill, S. J., & Mathews, C. K. (2016). Biochemistry: Concepts and connections. Pearson Education. • McMurry, J., Begley, T. P., & Begley, T. (2005). The organic chemistry of biological pathways. Roberts and Company Publishers. </video> <video> PyMOL 101, Lesson 7: Secondary structure H-bonding, measurement wizard, & names panel grouping Description: In this lesson, KP takes you on a deeper analysis of secondary structure. Building on the measurement techniques from Lesson 6, we’ll model an alpha helix, an antiparallel beta sheet, and a parallel beta sheet. We’ll analyze all three secondary structures to find out about the hydrogen bonding patterns that characterize each. 00:00 Intro 00:24 Setting up your workspace 00:52 Alpha helix modeling 01:34 The i+4 rule for alpha helices 03:32 Alpha helix backbone interactions with the measurement wizard 04:00 Grouping measurements 04:39 Measurement wizard – merge measurements 05:36 Antiparallel vs. parallel beta sheets 06:24 Modeling the antiparallel beta sheet 07:24 Modeling the parallel beta sheet 08:15 Parallel and antiparallel beta sheet structure comparison REFERENCES: • PDB ID: 1a0o • Welch, M., Chinardet, N., Mourey, L. et al. Structure of the CheY-binding domain of histidine kinase CheA in complex with CheY. Nat Struct Mol Biol 5, 25–29 (1998). https://doi.org/10.1038/nsb0198-25 </video> <video> PyMOL 101, Lesson 3: File Types and Saving – Publication Quality Figures & Scenes Description: In this lesson, KP takes you through the input and output PyMOL files, how to save your session, how to export a high-quality PNG image. Finally, we’ll learn to save scenes, preserving the different renderings and views as you work through this tutorial. 00:00 Intro 00:21 PDB and CIF files 01:41 Publication quality image guidelines and saving 04:41 Saving scenes in a PyMOL session REFERENCES • Rachel Kramer Green, Beginner’s Guide to PDB Structures and the PDBx/mmCIF Format https://pdb101.rcsb.org/learn/guide-to-understanding-pdb-data/beginner%E2%80%99s-guide-to-pdb-structures-and-the-pdbx-mmcif-format • PDB ID: 3uyn • Elder, I., Fisher, Z., Laipis, P. J., Tu, C., McKenna, R., & Silverman, D. N. (2007). Structural and kinetic analysis of proton shuttle residues in the active site of human carbonic anhydrase III. PROTEINS: Structure, Function, and Bioinformatics, 68(1), 337-343. ***COMMAND LINE CODE to recreate the Lesson 2 structure*** fetch 3UYN, type=pdb1, multiplex=1 select zn, resn zinc sele active, resi 5+7+62+64+67+94+96+119+199+200] show sticks, active zoom active select active_water, ((resi 5+7+62+64+67+94+96+119+199+200, resn Zn)around 3.3) and(resn HOH) hide nonbonded show spheres, active_water alter active_water, vdw=0.5 rebuild hide sticks, name c+o+n </video> <video> PyMOL 101, Lesson 6: Introduction to the measurement wizard & polar contacts, the N- & C-terminus Description: In this lesson, we’ll learn a PyMOL preset to display protein interfaces. Then, we’ll introduce the measurement wizard, and explore different types of molecular interactions. 00:00 Introduction and typical interaction distances 00:22 Interface preset 01:08 Peptide bond formation & the N- and C-terminus 02:10 Grayed out amino acids in the sequence display 02:30 Find polar contacts at the protein interface 03:09 The measurement wizard & van der Waals interactions 04:58 Polar vs. nonpolar amino acid side chains 05:26 Find polar contacts – a word of caution REFERENCES: • PDB ID: 1a0o • Welch, M., Chinardet, N., Mourey, L. et al. Structure of the CheY-binding domain of histidine kinase CheA in complex with CheY. Nat Struct Mol Biol 5, 25–29 (1998). https://doi.org/10.1038/nsb0198-25 • https://proteopedia.org/wiki/index.php/Non-covalent_interactions </video> <video> The Mechanisms of Glycolysis (Part 1) Description: Dr. KP takes you through the arrow pushing for the first 5 steps of glycolysis. 00:00 Introduction 00:12 Hexokinase 03:43 Glucose-6-phosphate isomerase 08:10 Phosphofructokinase 10:15 Aldolase 14:50 Triose phosphate isomerase REFERENCES: • Appling, D. R., Anthony-Cahill, S. J., & Mathews, C. K. (2016). Biochemistry: Concepts and connections. Pearson Education. • McMurry, J., Begley, T. P., & Begley, T. (2005). The organic chemistry of biological pathways. Roberts and Company Publishers. </video>

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Welcome! I'm KP, and I'm an organic chemist that loves making videos and sharing free chemistry and biochemistry resources. I hope you enjoy and learn something!

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