Introduction to Protein Structure through Homology ... · Introduction to Protein Structure through...

Undergraduate Educator Network Webinar

Introduction to Protein Structure through Homology Modeling Using Bioinformatics

Woon-Kai Low, PhDAssociate ProfessorSt. John’s University, College of Pharmacy &Health SciencesQueens, NY, 11439loww@stjohns.edu

3 credits (one semester) Associated lab (1 credit, 3 hours/week) Students:

– 3rd year toxicology majors (BS) http://www.stjohns.edu/academics/schools-and-colleges/college-pharmacy-and-health-

sciences/programs-and-majors/biomedical-sciences-bachelor-science

– 2nd year Clinical Laboratory Sciences (BS) http://www.stjohns.edu/academics/schools-and-colleges/college-pharmacy-and-health-

sciences/programs-and-majors/clinical-laboratory-sciences-bachelor-science

Molecular Toxicogenomics

Introduction to the molecular and genetic basis for human diversity

Impact on toxicological and pharmacological response

Scientific basis of personalized (precision medicine)

Molecular Toxicogenomics(3 credits, one semester)

Introduction (and review) of amino acids, and the four levels of protein structure

Introduction to the concept of homology Introduction to bioinformatics

Lab #2: Protein Structure and Homology

Image Source: Getty Images © SOT 2018

Resources (Part I):

Ajees, A. A., et al. (2012). "Structure of an As(III) S-adenosylmethionine methyltransferase: insights into the mechanism of arsenic biotransformation." Biochemistry 51(27): 5476-5485.https://www.ncbi.nlm.nih.gov/pubmed/22712827

Resources (Part II):RCSB PDB protein data bank

http://www.rcsb.org/pdb/home/home.do

Universal Protein Resource (UniProt)

http://www.uniprot.org/

Clustal Omega (sequence comparison software)

http://www.ebi.ac.uk/Tools/msa/clustalo/

NCBI National Center for Biotechnology Information

http://www.ncbi.nlm.nih.gov/

BLAST (Basic local alignment search tool)

http://blast.ncbi.nlm.nih.gov/Blast.cgi?CMD=Web&PAGE_TYPE=BlastHome

I. PDB entry for structure of arsenic methyltransferase (Cyanidioschyzon sp.)

II. UniProKB entries for arsenic methyltransferase

III. Sequence alignment of arsenic methyltransferase from different species using Clustal Omega

IV. NCBI BLAST using arsenic methyltrasferase Students maintain record of activities in lab

notebook

Student Activities

Search in PDB “arsenic methyltransferase”

I. Protein Data Bank

http://www.rcsb.org/pdb/home/home.do

Results – no structure for human protein (2 hits associated with Homo sapiens are related proteins)

I. Protein Data Bank

http://www.rcsb.org/pdb/home/home.do© SOT 2018

3 search hits from Cyanidioschyzon sp. (algae)

Ajees, A. A., et al. (2012). Biochemistry 51(27): 5476-5485.http://www.rcsb.org/pdb/results/results.do?tabtoshow=Current&qrid=37EECA42

Explore entry 4FSD (with arsenic ligand)

http://www.rcsb.org/pdb/explore/explore.do?structureId=4FSD

3D view – identify residues involved in binding

http://www.rcsb.org/pdb/ngl/ngl.do?pdbid=4FSD&bionumber=1

Sequence view

http://www.rcsb.org/pdb/explore/remediatedSequence.do?structureId=4FSD

II. Universal Protein Knowledgebase

Explore entries for arsenic methyltransferase from human, rat and mouse

Collect sequences for each in FASTA format

http://www.uniprot.org/uniprot/?query=AS3MT&sort=score

III. Clustal Sequence Alignment Using AS3MT

sequences from human, rat, mouse and Cyanidioschyzonsp.

https://www.ebi.ac.uk/Tools/msa/clustalo/

Note conservation surrounding binding pocket residues

Residues involved in function (co-ordination of ligands, arsenic)

IV. BLAST

https://blast.ncbi.nlm.nih.gov/Blast.cgi?CMD=Web&PAGE_TYPE=BlastHome

Explore the BLAST results

Final lab report – questions Bioinformatics – databases and their utility

(PDB vs. UniProtKB) Homology – evolutionary conservation of amino

acid sequence and protein function Clustal alignment results vs. BLAST search

results

Post-Lab Activities

Introduction to Protein Structure through Homology ... · Introduction to Protein Structure through...

Documents

Methods for Protein Structure Prediction Homology Modeling ...dspace.mit.edu/bitstream/handle/1721.1/96935/7-91j-spring-2004/... · Methods for Protein Structure Prediction Homology

COMPUTATIONAL REPRESENTATION OF PROTEIN SEQUENCES …etd.lib.metu.edu.tr/upload/12606997/index.pdf · COMPUTATIONAL REPRESENTATION OF PROTEIN SEQUENCES FOR HOMOLOGY DETECTION AND

Protein Homology Analysis for Function Prediction with

Role of C-reactive protein in osteoclastogenesis in ... · RESEARCH ARTICLE Open Access Role of C-reactive protein in osteoclastogenesis in rheumatoid arthritis Kyoung-Woon Kim1,

Construction of an A2a GPCR Model using Homology Comparative Protein Modeling

HOMOLOGY MODELING, STRUCTURAL ASSESSMENT AND … · 2018-04-23 · Research Article HOMOLOGY MODELING, STRUCTURAL ASSESSMENT AND DOCKING STUDY OF HEMAGGLUTININ PROTEIN OF H1N1 VIRUS

BASIC PROTEIN STRUCTURE PREDICTION FOR THE BIOLOGIST: …€¦ · class of protein structure prediction methods has appeared: protein threading. Homology modeling makes structure

Structure homology and interaction redundancy for …...Structure homology and interaction redundancy for discovering virus–host protein interactions Benoıˆt de Chassey 1,Laure`ne

PROSNET: INTEGRATING HOMOLOGY WITH MOLECULAR NETWORKS …psb.stanford.edu/psb-online/proceedings/psb17/wang_s.pdf · PROSNET: INTEGRATING HOMOLOGY WITH MOLECULAR NETWORKS FOR PROTEIN

A 33 kDa protein with sequence homology to the 'laminin binding … · 2005. 8. 31. · A 33 kDa protein with sequence homology to the 'laminin binding protein' is associated with

Oh hyung woon

Homology Modeling and Structure Prediction of Thioredoxin (TRX) Protein in Wheat (Triticum Aestivum L.)

Homology modeling and structure prediction of thioredoxin (TRX) protein … · Homology modeling and structure prediction of thioredoxin (TRX) protein in wheat (Triticum aestivum

Homology identification method that combines protein

Protein Structure Prediction: Homology Modeling & Threading/Fold Recognition D. Mohanty NII, New Delhi

Protein Families 1. sequence homology ― gene & protein Swiss Prot blastp 2. similar protein structure – includes S-S, 2 ndary structure patterns, 3D conformation

Persistent homology analysis of protein structure ... · Persistent homology analysis of protein structure, exibility and folding Kelin Xia 1 ;2Guo-Wei Wei 3 4 1Department of Mathematics

Homology Modelling of Protein-protein Complexes

RECURSIVE PROTEIN MODELING: A DIVIDE AND ...calla.rnet.missouri.edu/.../jbcb_recursive_modeling.pdfparative modeling or homology modeling) builds the structure of a query protein from

Persistent homology analysis of protein structure ... · PERSISTENT HOMOLOGY FOR PROTEIN continuously over a range of spatial scales. Unlike commonly used computational homology,