Using Computational Tools in Virtual Protein-Centric CUREs and UREs

Based on “Teasching Virtual Protein-Centric CUREs and UREs Using Computational Tools”

Introduction and Overview to the Tutorials Below

Phase 1: Developing a Research Proposal

Module 1: Using Primary Literature and Data Bases

Part 1 (Literature Background, PubMed), Part 2 (Using Blast), Part3 (Using Clustal Omega)

Module 2: Molecular Visualization

Module 3: What is a good research project: Hypothesis Development & Proposal

Phase 2: Preparing the Proteins

Module 4: Creating & Validating Models

Part 1 (Creating Mutants with PyMol), Part 2 (Creating Mutants with Phyre2), Part 3 (Refining the Structures), Part 3A(Using Galaxy Web to refine monomer and oligomer structures) Part 4 (Constructing Oligomers), Part 5 (MolProbity), Part 6 (Using Missense 3D)

Phase 3: Computational Experimental Approaches to Explore the Questions developed from the Hypothesis

Module 5: Exploring Titratable Groups in a Protein

Module 6: Exploring Small Molecule Ligand Binding

Part 1 (Submitting to SwissDock), Part 2(Exploring Clusters-PyMol & Poses-Chimera)

Module 7: Exploring Protein-Protein Interactions

Module 8: Detecting and Exploring Potential Binding Sites in a Protein

Module 9: Structure-Activity Relationships of Ligand Binding & Drug Design

Papers for Journal Clubs on the Computational Techniques Presented here:

Kelley,L.A., Mezulis,S., Yates,, C.M., Wass M. &  Sternberg, M.J.E. “The Phyre2 web portal for protein modeling, prediction and analysis” Nature Protocols volume 10, pages845–858(2015) https://pubmed.ncbi.nlm.nih.gov/25950237/

Bhattacharya D “refineD: improved protein structure refinement using machine learning based restrained relaxation”.Bioinformatics. 2019 Sep 15;35(18):3320-3328. https://pubmed.ncbi.nlm.nih.gov/30759180/

Williams et al. (2018) MolProbity: More and better reference data for improved all-atom structure validation. Protein Science 27: 293-315. https://pubmed.ncbi.nlm.nih.gov/29067766/

Ramu Anandakrishnan, Boris Aguilar and Alexey V. Onufriev, "H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulation", Nucleic Acids Res., 40(W1):W537-541. (2012) https://pubmed.ncbi.nlm.nih.gov/22570416/

Aurélien Grosdidier,1 Vincent Zoete,1,* and Olivier Michielin “SwissDock, a protein-small molecule docking web service based on EADock DSS” Nucleic Acids Res. 2011 Jul 1; 39(Web Server issue): W270–W277 https://pubmed.ncbi.nlm.nih.gov/21624888/

Gaoqi WengErcheng WangZhe WangHui LiuFeng ZhuDan LiTingjun Hou “HawkDock: a web server to predict and analyze the protein–protein complex based on computational docking and MM/GBSA” Nucleic Acids Research, Volume 47, Issue W1, (2019) https://pubmed.ncbi.nlm.nih.gov/31106357/

Yu J, Zhou Y, Tanaka I, Yao M “Roll: a new algorithm for the detection of protein pockets and cavities with a rolling probe sphere”. Bioinformatics. 2010 Jan 1;26(1):46-52. https://pubmed.ncbi.nlm.nih.gov/19846440/

Using Computational Tools in Virtual Molecular Biology Laboratories

Bioinformatics Workshop Template

SnapGene Workshop Template

Rubrics

Rubric for Noncovalent interactions

Rubric for Hypothesis Development and Proposal

Rubric for Presentations

Hints for Using Virtual Communication Approaches to Build a Research Community