Understanding protein-ligand binding at the molecular level: Using swap-based methods to visualise binding free energy components
|
|
- Abraham Carroll
- 6 years ago
- Views:
Transcription
1 Understanding protein-ligand binding at the molecular level: Using swap-based methods to visualise binding free energy components Christopher Woods, School of Chemistry, University of Bristol Advanced Computing Research Centre
2 Part 1: Protein-Ligand Binding ΔGbind Protein Complex Ligand
3 Biochemistry occurs in the aqueous phase
4 Absolute Binding Free Energy Calculations Protein(aq) Ligand(aq) ΔGbind Water (aq) Complex(aq)
5 Double Decoupling / Double Annihilation Protein(aq) ΔGbound Complex(aq) ΔGbind Ligand(aq) ΔGfree Water (aq)
6 WaterSwap Absolute binding free energy method Recognises the competition between the ligand and water for the protein binding site Woods et al., J. Chem. Phys., 134, , 2011 Woods et al., Faraday Trans., 169, , 2014
7 WaterSwap Protein(aq) Ligand(aq) ΔGbind Water (aq) Complex(aq)
8 Waterswap uses a λ-coordinate to swap a ligand and a water cluster between a protein box and a water box Protein Box Water Box
9 Waterswap uses a λ-coordinate to swap a ligand and a water cluster between a protein box and a water box Protein Box 100% 0% λ=0.0 Water Box
10 Waterswap uses a λ-coordinate to swap a ligand and a water cluster between a protein box and a water box Protein Box 80% 20% λ=0.2 Water Box
11 Waterswap uses a λ-coordinate to swap a ligand and a water cluster between a protein box and a water box Protein Box 50% 50% λ=0.5 Water Box
12 Waterswap uses a λ-coordinate to swap a ligand and a water cluster between a protein box and a water box Protein Box 20% 80% λ=0.8 Water Box
13 Waterswap uses a λ-coordinate to swap a ligand and a water cluster between a protein box and a water box Protein Box 0% 100% λ=1.0 Water Box
14 Integrating the free energy along this λ-coordinate leads directly to the absolute binding free energy
15 Integrating the free energy along this λ-coordinate leads directly to the absolute binding free energy ΔGbind
16 Testing against experiment
17 Simulation / kcal mol R 2 = Experiment / kcal mol -1
18 Waterswap uses a λ-coordinate to swap a ligand and a water cluster between a protein box and a water box Protein Box Water Box
19 per- Absolute binding free energy can be decomposed to residue contributions Protein Box Water Box
20 Residues can be color-coded based on whether they stabilise binding the ligand, or binding water Phe227 Phe227 Blue = Stabilises the ligand Red = Stabilises water
21 Can also decompose to visualise contribution from active-site water molecules Glu192 Asp189 Blue = Stabilises the ligand Red = Stabilises water Glu192
22 Displacing water by replacing m-chlorobenzyl with benzamidine systematically strengthens binding Christopher J. Woods, Maturos Malaisree, Julien Michel, Ben Long, Simon McIntosh-Smith and Adrian J. Mulholland Binding Affinity / kcal mol Ligand m-chlorobenzyl benzamidine gure S1. Experimentally measured binding affinities for the 10 ligands studied in this rk (m-chlorobenzyl) Muley, L, and et for al., the J. ten Med. benzamidine Chem., 53, analogs , Binding 2010 affinities are taken m Muley et al., doi: /jm (reference 32 in our paper).
23 Part 2: Mutation and Drug Resistance Wildtype Drug Resistant Mutant Woods et al., Biochemistry, 51, , 2012 Woods et al., Biochemistry, 52, , 2013
24 ProteinSwap Absolute binding free energy method comparing different protein mutants Recognises the competition between a wildtype and mutant protein for which one will bind the ligand, and which will bind water
25 ProteinSwap Wildtype Box Mutant Box (R292K)
26 ProteinSwap Wildtype Box 100% λ=0.0 Mutant Box (R292K) 0%
27 ProteinSwap Wildtype Box 80% λ=0.2 Mutant Box (R292K) 20%
28 ProteinSwap Wildtype Box 50% λ=0.5 Mutant Box (R292K) 50%
29 ProteinSwap Wildtype Box 20% λ=0.8 Mutant Box (R292K) 80%
30 ProteinSwap Wildtype Box 0% λ=1.0 Mutant Box (R292K) 100%
31 Integrating the free energy along this λ-coordinate leads directly to the preference for the wildtype or mutant to bind the ligand or water cluster Free Energy / kcal mol WT R292K 8.3 ± 0.8 kcal mol λ *Peramivir bound to WT and R292K H1N neuraminidase
32 Residue-based free energy decomposition Wildtype Blue = Stabilises the ligand R292K Mutant Red = Stabilises water
33 Difference in decomposition highlights impact of mutation R292K Mutant Blue = Stronger binding in mutant Red = Weaker binding in mutant
34 Comparing WT to E119G: E119G is resistant to peramivir D151 E119G R118 Peramivir = 3.0 ± 1.4 kcal mol-1 Blue = Stronger binding in mutant Red = Weaker binding in mutant
35 Comparing WT to E119G: E119G is not resistant to oseltamivir D151 E119G R118 Peramivir = 3.0 ± 1.4 kcal mol-1 Blue = Stronger binding in mutant Oseltamivir = 0.6 ± 0.8 kcal mol-1 Red = Weaker binding in mutant
36 WaterSwap and (soon) ProteinSwap are free command line tools available at
37 WaterSwap built into Flare
38 Conclusions WaterSwap and ProteinSwap let you rationalise protein-ligand binding at the molecular level ProteinSwap enables the effect of protein mutation on drug binding to be calculated and visualised Free command-line tool Commercial graphical interface
39 Acknowledgements Maturos Malaisree for setting up, running and analysing the simulations EPSRC and Cresset for funding Advanced Computing Research Centre for providing early access to BlueCrystal Phase4
40 Integrating the free energy along this λ-coordinate leads directly to the preference for the wildtype or mutant to bind the ligand or water cluster Free Energy / kcal mol WT R292K 8.3 ± 0.8 kcal mol λ *Peramivir bound to WT and R292K H1N neuraminidase
41 Mutant Wildtype is the negative of Wildtype Mutant 16 Free Energy / kcal mol R292K WT -7.7 ± 1.2 kcal mol λ *Peramivir bound to WT and R292K H1N neuraminidase
42 Closing Triangles Free Energy is a State Function R152K Wildtype 8.3±0.8 kcal mol -1 R292K E119G *Peramivir bound to WT, R292K, R152K and E119 H1N neuraminidase
43 Peramivir binding to WT and R292K mutant H1N1 NA Wildtype Blue = Stronger binding in mutant R292K Mutant Red = Weaker binding in mutant
44 Oseltamivir binding to WT and R292K mutant H1N1 NA Wildtype Blue = Stronger binding in mutant R292K Mutant Red = Weaker binding in mutant
45
46
47
48
49
50
51
SUPPLEMENTARY INFORMATION. Computational Assay of H7N9 Influenza Neuraminidase Reveals R292K Mutation Reduces Drug Binding Affinity
SUPPLEMENTARY INFORMATION Computational Assay of H7N9 Influenza Neuraminidase Reveals R292K Mutation Reduces Drug Binding Affinity Christopher Woods 1, Maturos Malaisree 1, Ben Long 2, Simon McIntosh-Smith
More informationSupplementary Figure 1 (previous page). EM analysis of full-length GCGR. (a) Exemplary tilt pair images of the GCGR mab23 complex acquired for Random
S1 Supplementary Figure 1 (previous page). EM analysis of full-length GCGR. (a) Exemplary tilt pair images of the GCGR mab23 complex acquired for Random Conical Tilt (RCT) reconstruction (left: -50,right:
More informationDetergent solubilised 5 TMD binds pregnanolone at the Q245 neurosteroid potentiation site.
Supplementary Figure 1 Detergent solubilised 5 TMD binds pregnanolone at the Q245 neurosteroid potentiation site. (a) Gel filtration profiles of purified 5 TMD samples at 100 nm, heated beforehand for
More informationFinding the Sweet Spot- Mechanism Guided Design of Glycosidase Inhibitors. Jahnabi Roy CHEM 575 Seminar 11/01/12
Finding the Sweet Spot- Mechanism Guided Design of Glycosidase Inhibitors Jahnabi Roy CHEM 575 Seminar 11/01/12 Glycans and Glycosyl Hydrolases http://cellbiology.med.unsw.edu.au/units/science/lecture0803.htm
More informationExcerpt from J. Mol. Biol. (2002) 320, :
Excerpt from J. Mol. Biol. (2002) 320, 1095 1108: Crystal Structure of the Ternary Complex of the Catalytic Domain of Human Phenylalanine Hydroxylase with Tetrahydrobiopterin and 3-(2-Thienyl)-L-alanine,
More informationStructure/Function of Biomolecules (Chem 240) Comparing Neuraminidase to the period at the end of a sentence.
Comparing Neuraminidase to the period at the end of a sentence. Measure the distance between two atoms on either side of the enzyme. Select both atoms and from the toolbar, choose... tools...structure
More informationThe MOLECULES of LIFE
The MOLECULES of LIFE Physical and Chemical Principles Solutions Manual Prepared by James Fraser and Samuel Leachman Chapter 16 Principles of Enzyme Catalysis Problems True/False and Multiple Choice 1.
More informationTable S1: Kinetic parameters of drug and substrate binding to wild type and HIV-1 protease variants. Data adapted from Ref. 6 in main text.
Dynamical Network of HIV-1 Protease Mutants Reveals the Mechanism of Drug Resistance and Unhindered Activity Rajeswari Appadurai and Sanjib Senapati* BJM School of Biosciences and Department of Biotechnology,
More informationPhenylketonuria (PKU) Structure of Phenylalanine Hydroxylase. Biol 405 Molecular Medicine
Phenylketonuria (PKU) Structure of Phenylalanine Hydroxylase Biol 405 Molecular Medicine 1998 Crystal structure of phenylalanine hydroxylase solved. The polypeptide consists of three regions: Regulatory
More informationTransient β-hairpin Formation in α-synuclein Monomer Revealed by Coarse-grained Molecular Dynamics Simulation
Transient β-hairpin Formation in α-synuclein Monomer Revealed by Coarse-grained Molecular Dynamics Simulation Hang Yu, 1, 2, a) Wei Han, 1, 3, b) Wen Ma, 1, 2 1, 2, 3, c) and Klaus Schulten 1) Beckman
More informationSupplementary Figure-1. SDS PAGE analysis of purified designed carbonic anhydrase enzymes. M1-M4 shown in lanes 1-4, respectively, with molecular
Supplementary Figure-1. SDS PAGE analysis of purified designed carbonic anhydrase enzymes. M1-M4 shown in lanes 1-4, respectively, with molecular weight markers (M). Supplementary Figure-2. Overlay of
More informationBIOCHEMISTRY 460 FIRST HOUR EXAMINATION FORM A (yellow) ANSWER KEY February 11, 2008
WRITE YOUR AND I.D. NUMBER LEGIBLY ON EVERY PAGE PAGES WILL BE SEPARATED FOR GRADING! CHECK TO BE SURE YOU HAVE 6 PAGES, (print): ANSWERS INCLUDING COVER PAGE. I swear/affirm that I have neither given
More informationJournal of Chemical and Pharmaceutical Research, 2012, 4(6): Research Article
vailable online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 01, 4(6):3107-3115 Research rticle ISSN : 0975-7384 CODEN(US) : JCPRC5 Comparative study of interaction of benzene sulfonamides
More informationList of Figures. List of Tables
Supporting Information for: Signaling Domain of Sonic Hedgehog as Cannibalistic Calcium-Regulated Zinc-Peptidase Rocio Rebollido-Rios 1, Shyam Bandari 3, Christoph Wilms 1, Stanislav Jakuschev 1, Andrea
More informationSUPPORTING INFORMATION FOR. A Computational Approach to Enzyme Design: Using Docking and MM- GBSA Scoring
SUPPRTING INFRMATIN FR A Computational Approach to Enzyme Design: Predicting ω- Aminotransferase Catalytic Activity Using Docking and MM- GBSA Scoring Sarah Sirin, 1 Rajesh Kumar, 2 Carlos Martinez, 2
More informationSupplementary Material
Supplementary Material Materials and methods Enzyme assay The enzymatic activity of -glucosidase toward salicin was measured with the Miller method (Miller, 1959) using glucose as the standard. A total
More informationSUPPLEMENTARY INFORMATION
High-speed atomic force microscopy shows that annexin V stabilizes membranes on the second timescale Atsushi Miyagi, Chris Chipot, Martina Rangl & Simon Scheuring Supplementary Movies: Supplementary Movie
More informationSupporting material. Membrane permeation induced by aggregates of human islet amyloid polypeptides
Supporting material Membrane permeation induced by aggregates of human islet amyloid polypeptides Chetan Poojari Forschungszentrum Jülich GmbH, Institute of Complex Systems: Structural Biochemistry (ICS-6),
More informationSudha Srivastava. National Facility for High Field NMR Tata Institute of Fundamental Research, Mumbai, India.
Novel inhibitor by modifying oseltamivir, based on neuraminidase structure, for treating drug-resistant H5N1 virus using molecular docking, NMR and DSC methods. Sudha Srivastava National Facility for High
More informationArginine side chain interactions and the role of arginine as a mobile charge carrier in voltage sensitive ion channels. Supplementary Information
Arginine side chain interactions and the role of arginine as a mobile charge carrier in voltage sensitive ion channels Craig T. Armstrong, Philip E. Mason, J. L. Ross Anderson and Christopher E. Dempsey
More informationMultiple-Choice Questions Answer ALL 20 multiple-choice questions on the Scantron Card in PENCIL
Multiple-Choice Questions Answer ALL 20 multiple-choice questions on the Scantron Card in PENCIL For Questions 1-10 choose ONE INCORRECT answer. 1. Which ONE of the following statements concerning the
More informationPatterns of hemagglutinin evolution and the epidemiology of influenza
2 8 US Annual Mortality Rate All causes Infectious Disease Patterns of hemagglutinin evolution and the epidemiology of influenza DIMACS Working Group on Genetics and Evolution of Pathogens, 25 Nov 3 Deaths
More informationInvestigation of the binding of spermine and derivative polyamines on the 1U6M active site in the presence of Acetyl coenzyme-a
Investigation of the binding of spermine and derivative polyamines on the 1U6M active site in the presence of Acetyl coenzyme-a Lindsay Mitchell lm04575n@pace.edu Pace University NYC Department of Chemistry
More informationVision. Vision. Vision. Chem Lecture 10 Signal Transduction & Sensory Systems Part 6. Rod cells. E = hν = hc λ
Chem 452 - Lecture 10 Signal Transduction & Sensory Systems Part 6 Question of the Day: Who has better color vision, a human or a mantis shrimp? involves the transduction of light energy to an nerve signal.
More informationSUPPLEMENTARY INFORMATION
SUPPLEMENTARY INFORMATION doi:10.1038/nature22394 Supplementary Table 1 Observed intermolecular interactions within the GLP-1:GLP-1R TMD interface. Superscripts refer to the Wootten residue numbering system
More informationIntroduction to Protein Structure Collection
Introduction to Protein Structure Collection Teaching Points This collection is designed to introduce students to the concepts of protein structure and biochemistry. Different activities guide students
More informationWorkshop on Analysis and prediction of contacts in proteins
Workshop on Analysis and prediction of contacts in proteins 1.09.09 Eran Eyal 1, Vladimir Potapov 2, Ronen Levy 3, Vladimir Sobolev 3 and Marvin Edelman 3 1 Sheba Medical Center, Ramat Gan, Israel; Departments
More informationSTRUCTURE OF A UBIQUITIN-LOADED HECT LIGASE REVEALS THE MOLECULAR BASIS FOR CATALYTIC PRIMING SUPPLEMENTARY INFORMATION
STRUCTURE OF A UBIQUITINLOADED ECT LIGASE REVEALS TE MOLECULAR BASIS FOR CATALYTIC PRIMING Elena Maspero 1, Eleonora Valentini 1, Sara Mari 1, Valentina Cecatiello 2, Paolo Soffientini 1, Sebastiano Pasqualato
More informationCombining molecular modelling with experiments: Sulfonylureas and glinides as new PPARγ agonists
Combining molecular modelling with experiments: Sulfonylureas and glinides as new PPARγ agonists Marco Scarsi Biozentrum - Swiss Institute of Bioinformatics Drug discovery and development 12-15 years of
More informationThe Binding Mode of by Electron Crystallography
The Binding Mode of Epothilone A on α,β-tubulin by Electron Crystallography James H. Nettles, Huilin Li, Ben Cornett, Joseph M. Krahn, James P. Snyder, Kenneth H. Downing Science, Volume 305, August 6,
More informationInteractions of Polyethylenimines with Zwitterionic and. Anionic Lipid Membranes
Interactions of Polyethylenimines with Zwitterionic and Anionic Lipid Membranes Urszula Kwolek, Dorota Jamróz, Małgorzata Janiczek, Maria Nowakowska, Paweł Wydro, Mariusz Kepczynski Faculty of Chemistry,
More informationOverview of Pharmacodynamics. Psyc 472 Pharmacology of Psychoactive Drugs. Pharmacodynamics. Effects on Target Binding Site.
Pharmacodynamics Overview of Pharmacodynamics Psychology 472: Pharmacology of Psychoactive Drugs Generally is defined as effects of drugs on a systems Can be associated with any system Neural, Heart, Liver,
More informationFinal Report. Identification of Residue Mutations that Increase the Binding Affinity of LSTc to HA RBD. Wendy Fong ( 方美珍 ) CNIC; Beijing, China
Final Report Identification of Residue Mutations that Increase the Binding Affinity of LSTc to HA RBD Wendy Fong ( 方美珍 ) CNIC; Beijing, China Influenza s Viral Life Cycle 1. HA on virus binds to sialic
More informationKey Concepts. Learning Objectives
Lectures 8 and 9: Protein Function, Ligand Binding -- Oxygen Binding and Allosteric Regulation in Hemoglobin [PDF] Reading: Berg, Tymoczko & Stryer, Chapter 7, pp. 183-199 problems in textbook: chapter
More informationESI and MALDI Mass Spectrometry. S. Sankararaman Department of Chemistry Indian Institute of Technology Madras Chennai
ESI and MALDI Mass Spectrometry S. Sankararaman Department of Chemistry Indian Institute of Technology Madras Chennai 600036 sanka@iitm.ac.in MODULE 22 ESI-Q MASS SPECTROMETRY - examples Mol. Wt = 1140
More informationQuantitative Predictions of Binding Free Energy Changes in Drug-Resistant Influenza Neuraminidase
Quantitative Predictions of Binding Free Energy Changes in Drug-Resistant Influenza Neuraminidase Daniel R. Ripoll 1, Ilja V. Khavrutskii 1, Sidhartha Chaudhury 1, Jin Liu 1, Robert A. Kuschner 2, Anders
More information7.014 Problem Set 2 Answers to this problem set are to be turned in. Problem sets will not be accepted late. Solutions will be posted on the web.
MIT Department of Biology 7.014 Introductory Biology, Spring 2005 Name: Section : 7.014 Problem Set 2 Answers to this problem set are to be turned in. Problem sets will not be accepted late. Solutions
More informationStructure of the measles virus hemagglutinin bound to the CD46 receptor. César Santiago, María L. Celma, Thilo Stehle and José M.
Supporting Figures and Table for Structure of the measles virus hemagglutinin bound to the CD46 receptor César Santiago, María L. Celma, Thilo Stehle and José M. Casasnovas This PDF file includes: Supplementary
More informationAnti-influenza (M2 and NA) Drugs
Anti-influenza (M2 and NA) Drugs Alan J. Hay MRC National Institute for Medical Research, London Summer School on Influenza Siena 1-5 August 2011 Antiviral drugs licensed for use against influenza M2 (Flu
More informationNEXT GENERATION SEQUENCING OPENS NEW VIEWS ON VIRUS EVOLUTION AND EPIDEMIOLOGY. 16th International WAVLD symposium, 10th OIE Seminar
NEXT GENERATION SEQUENCING OPENS NEW VIEWS ON VIRUS EVOLUTION AND EPIDEMIOLOGY S. Van Borm, I. Monne, D. King and T. Rosseel 16th International WAVLD symposium, 10th OIE Seminar 07.06.2013 Viral livestock
More informationFlu, Avian Flu and emerging aspects (H1N1 resistance)
EU-CIS Seminar New trends in Infectious Diseases 26 28 November 2008 / Lyon, France Flu, Avian Flu and emerging aspects (H1N1 resistance) Pr. Florence MORFIN FRE 3011 Université Lyon 1 - CNRS Laboratory
More informationBMC Biology. Open Access. Abstract. BioMed Central
BMC Biology BioMed Central Research article A modular interface of IL-4 allows for scalable affinity without affecting specificity for the IL-4 receptor Michael Kraich 1, Markus Klein 1, Edwin Patiño 1,
More informationSupplementary Materials. High affinity binding of phosphatidylinositol-4-phosphate. by Legionella pneumophila DrrA
Supplementary Materials High affinity binding of phosphatidylinositol-4-phosphate by Legionella pneumophila DrrA Running title: Molecular basis of PtdIns(4)P-binding by DrrA Stefan Schoebel, Wulf Blankenfeldt,
More informationFinal Exam Chemistry 391 Structural Biochemistry Fall Do not open the exam until ready to begin! Rules of the Game:
Name Practice for 2018 Final Exam Chemistry 391 Structural Biochemistry Fall 2016 Do not open the exam until ready to begin! ules of the Game: This is a take-home Exam. The exam is due on Thursday, December
More informationA Combinatorial approach: To design inhibitory molecules on Hemagglutinin protein of H1N1 virus (Swine Flu)
www.bioinformation.net Hypothesis Volume 9(11) A Combinatorial approach: To design inhibitory molecules on Hemagglutinin protein of H1N1 virus (Swine Flu) Chekkara Venkata Satya Siva Prasad*, Kamal Kumar
More informationFile name: Supplementary Information Description: Supplementary figures and supplementary tables. File name: Peer review file Description:
File name: Supplementary Information Description: Supplementary figures and supplementary tables. File name: Peer review file Description: Supplementary Figure 1. Schematic of Ras biochemical coupled assay.
More informationMolecular Dynamics of HIV-1 Reverse Transcriptase
Molecular Dynamics of HIV-1 Reverse Transcriptase Abderrahmane Benghanem Rensselaer Polytechnic Institute,Troy, NY Mentor: Dr. Maria Kurnikova Carnegie Mellon, Pittsburgh PA Outline HIV-1 Reverse Transcriptase
More informationInnate-adaptive immunity duo as a regimen for conferring rapid-sustained-broad protection against pathogens
Innate-adaptive immunity duo as a regimen for conferring rapid-sustained-broad protection against pathogens De-chu Christopher Tang, PhD VaxDome LLC Dallas, Texas September 29, 15 A litany of demands for
More informationNature Structural and Molecular Biology: doi: /nsmb Supplementary Figure 1
Supplementary Figure 1 Mutational analysis of the SA2-Scc1 interaction in vitro and in human cells. (a) Autoradiograph (top) and Coomassie stained gel (bottom) of 35 S-labeled Myc-SA2 proteins (input)
More informationCrystallization-grade After D After V3 cocktail. Time (s) Time (s) Time (s) Time (s) Time (s) Time (s)
Ligand Type Name 6 Crystallization-grade After 447-52D After V3 cocktail Receptor CD4 Resonance Units 5 1 5 1 5 1 Broadly neutralizing antibodies 2G12 VRC26.9 Resonance Units Resonance Units 3 1 15 1 5
More informationUNIVERSITY OF GUELPH CHEM 4540 ENZYMOLOGY Winter 2005 Quiz #2: March 24, 2005, 11:30 12:50 Instructor: Prof R. Merrill ANSWERS
UNIVERSITY F GUELPH CHEM 4540 ENZYMLGY Winter 2005 Quiz #2: March 24, 2005, 11:30 12:50 Instructor: Prof R. Merrill ANSWERS Instructions: Time allowed = 80 minutes. Total marks = 30. This quiz represents
More informationSupplementary Information
Supplementary Information Structural Basis of Sialidase in Complex with Geranylated Flavonoids as Potent Natural Inhibitors Youngjin Lee, a,b Young Bae Ryu, d Hyung-Seop Youn, a,b Jung Keun Cho, e Young
More informationSupplementary Information
Supplementary Information Two common structural motifs for TCR recognition by staphylococcal enterotoxins Karin Erica Johanna Rödström 1, Paulina Regenthal 1, Christopher Bahl 2, Alex Ford 2, David Baker
More informationHOMEWORK II and Swiss-PDB Viewer Tutorial DUE 9/26/03 62 points total. The ph at which a peptide has no net charge is its isoelectric point.
BIOCHEMISTRY I HOMEWORK II and Swiss-PDB Viewer Tutorial DUE 9/26/03 62 points total 1). 8 points total T or F (2 points each; if false, briefly state why it is false) The ph at which a peptide has no
More informationInfluenza antiviral susceptibility: methods and challenges to detect resistant virus
SARINet Pan-American Health Organization - PAHO Influenza antiviral susceptibility: methods and challenges to detect resistant virus Brazilian experience Paola Cristina Resende, PhD Researcher National
More informationExploring Energy and Fitness Landscapes of Proteins
Exploring Energy and Fitness Landscapes of Proteins! Computer Simulations in Chemistry and Biophysics! Protein-Ligand Binding: structure based drug design! HIV Family and Kinase Family Protein Targets!
More informationAppendix. Table of Contents
Appendix Table of Contents Appendix Figures Figure S1: Gp78 is not required for the degradation of mcherry-cl1 in Hela Cells. Figure S2: Indel formation in the MARCH6 sgrna targeted HeLa clones. Figure
More informationLife Science 1A Final Exam. January 19, 2006
ame: TF: Section Time Life Science 1A Final Exam January 19, 2006 Please write legibly in the space provided below each question. You may not use calculators on this exam. We prefer that you use non-erasable
More informationInsights into the Giardia intestinalis Enolase and Human Plasminogen interaction
Electronic Supplementary Material (ESI) for Molecular BioSystems. This journal is The Royal Society of Chemistry 2017 Supplementary Information Insights into the Giardia intestinalis Enolase and Human
More informationPrevious Class. Today. Term test I discussions. Detection of enzymatic intermediates: chymotrypsin mechanism
Term test I discussions Previous Class Today Detection of enzymatic intermediates: chymotrypsin mechanism Mechanistic Understanding of Enzymemediated Reactions Ultimate goals: Identification of the intermediates,
More informationChapter VI. Increased affinity in the complex of yeast cytochrome c and cytochrome c peroxidase
Chapter VI Increased affinity in the complex of yeast cytochrome c and cytochrome c peroxidase Chapter VI Abstract We report the study of T12A Cyt c CcP complex using isothermal titration calorimetry (ITC),
More informationSupplementary Figure 1. Heavy chain sequences of 2G1 and 8M2 aligned with V H 1-69
Supplementary Figure 1. Heavy chain sequences of 2G1 and 8M2 aligned with V H 1-69 germline gene sequence. 2G1 and 8M2 acquired 14 and 18 mutations from the germline gene sequence, respectively. In 2G1,
More information2) Cases and controls were genotyped on different platforms. The comparability of the platforms should be discussed.
Reviewers' Comments: Reviewer #1 (Remarks to the Author) The manuscript titled 'Association of variations in HLA-class II and other loci with susceptibility to lung adenocarcinoma with EGFR mutation' evaluated
More informationCellular Neurophysiology I Membranes and Ion Channels
Cellular Neurophysiology I Membranes and Ion Channels Reading: BCP Chapter 3 www.bioelectriclab All living cells maintain an electrical potential (voltage) across their membranes (V m ). Resting Potential
More informationAcid/Base chemistry. NESA Biochemistry Fall 2001 Review problems for the first exam. Complete the following sentences
1 NESA Biochemistry Fall 2001 eview problems for the first exam Acid/Base chemistry 1. 2 3 is a weak acid. 2. The anion of a weak acid is a weak base 3. p is the measure of a solutions acidity. 4. 3 and
More informationMolecular Dynamics of Sialic Acid Analogues and their Interaction with Influenza Hemagglutinin
Research Papers www.ijpsonline.com Molecular Dynamics of Sialic Acid Analogues and their Interaction with Influenza Hemagglutinin T. FEMLIN BLESSIA, V. S. RAPHEAL 1 AND D. J. S. SHARMILA* Department of
More informationSupplementary Information A Hydrophobic Barrier Deep Within the Inner Pore of the TWIK-1 K2P Potassium Channel Aryal et al.
Supplementary Information A Hydrophobic Barrier Deep Within the Inner Pore of the TWIK-1 K2P Potassium Channel Aryal et al. Supplementary Figure 1 TWIK-1 stability during MD simulations in a phospholipid
More informationReview Influenza virus susceptibility and resistance to oseltamivir
Review Influenza virus susceptibility and resistance to oseltamivir Fred Y Aoki 1, Guy Boivin 2 and Noel Roberts 3 * Antiviral Therapy 12:603 616 1 Department of Medical Microbiology, University of Manitoba,
More informationBiologisch-chemisches Praktikum, Teil B Peptide and protein chemistry
Biologisch-chemisches Praktikum, Teil B 270042 Peptide and protein chemistry Part 2: Peptide synthesis (protease inhibitor) Protein labeling Protease inhibition assay Riboflavin analog: pk a change upon
More informationSupplementary information Common molecular mechanism of amyloid pore formation by Alzheimer s -amyloid peptide and -synuclein
1 Supplementary information Common molecular mechanism of amyloid pore formation by Alzheimer s -amyloid peptide and -synuclein by Coralie Di Scala, Nouara Yahi, Sonia Boutemeur, Alessandra Flores, Léa
More informationTable S1. X-ray data collection and refinement statistics
Table S1. X-ray data collection and refinement statistics Data collection H7.167 Fab-Sh2/H7 complex Beamline SSRL 12-2 Wavelength (Å) 0.97950 Space group I2 1 3 Unit cell parameters (Å, º) a = b = c=207.3,
More informationInfluenza virus.
INFLUENZA VIRUS Adapté en partie des exposés de la Chaire Franqui 2003 "Antiviral drugs and Discoveries in Medicine" Prof. E. De Clercq, KU-Leuven http://www.md.ucl.ac.be/chaire-francqui/ Influenza virus
More informationProtein Structure and Computational Biology, Good morning and welcome!
Protein Structure and Computational Biology, 27617 Good morning and welcome! Program 9.00-9.30 Introduction to the course 9.30-9.40 Break 9.40-10.00 Introduction to influenza a recurring case story 10.00-10.10
More informationVIRTUAL SCREENS WITH MULTIPLE RECEPTOR CONFORMATIONS. Rob Swift, UCI Wednesday, August 3, 2011
VIRTUAL SCREENS WITH MULTIPLE RECEPTR CNFRMATINS Rob Swift, UCI Wednesday, August 3, 2011 utline verview of multi receptor virtual screening in CADD Case studies 1. Trypanosoma brucei RNA editing ligase
More informationIncorporation of photo-caged lysine (pc-lys) at K273 of human LCK allows specific control of the enzyme activity.
Supplementary Figure 1 Incorporation of photo-caged lysine (pc-lys) at K273 of human LCK allows specific control of the enzyme activity. (a) Modeling of the kinase domain of LCK with ATP (left) or pc-lys
More informationTargeting PPIs in Oncology using a Fragment-Based Drug Discovery Approach Justin F. Bower CRUK Beatson Institute
Targeting PPIs in Oncology using a Fragment-Based Drug Discovery Approach Justin F. Bower CRUK Beatson Institute Cancer Research UK Beatson Institute Establish an outstanding basic research programme into
More informationLESSON 4.5 WORKBOOK. How do viruses adapt Antigenic shift and drift and the flu pandemic
DEFINITIONS OF TERMS Gene a particular sequence of DNA or RNA that contains information for the synthesis of a protien or RNA molecule. For a complete list of defined terms, see the Glossary. LESSON 4.5
More informationDigestion in the Presence of Bile Salt Micelles* Wallace V. Crandall and Mark E. Lowe
JBC Papers in Press. Published on January 16, 2001 as Manuscript M009986200 Colipase Residues Glu 64 and Arg 65 are Essential for Normal Lipase Mediated Fat Digestion in the Presence of Bile Salt Micelles*
More informationLigand binding preferences probed by ESI MS and amide H/D exchange
Ligand binding preferences probed by ESI MS and amide H/D exchange Hui Xiao; Benjamin W. Benson; Stephen J. Eyles; Igor A. Kaltashov Department of Chemistry, University of Massachusetts, Amherst, MA 01003
More information3.2 Ligand-Binding at Nicotinic Acid Receptor Subtypes GPR109A/B
3.2 Ligand-Binding at Nicotinic Acid Receptor Subtypes GPR109A/B 3.2.1 Characterization of the Ligand Binding Site at GPR109A Receptor Ligands of GPR109A Receptor are Carboxylic Acids Nicotinic acid (pyridine-3-carboxylic
More information1. Measurement of the rate constants for simple enzymatic reaction obeying Michaelis- Menten kinetics gave the following results: =3x10-5 = 30μM
1. Measurement of the rate constants for simple enzymatic reaction obeying Michaelis- Menten kinetics gave the following results: k 1 = 2 x 10 8 M -1 s -1, k 2 = 1 x 10 3 s -1, k 3 = 5 x 10 3 s -1 a) What
More informationENZYMES: CLASSIFICATION, STRUCTURE
ENZYMES: CLASSIFICATION, STRUCTURE Enzymes - catalysts of biological reactions Accelerate reactions by a millions fold Common features for enzymes and inorganic catalysts: 1. Catalyze only thermodynamically
More informationPredicting antigenic sites of hemagglutinin-neuraminidase glycoprotein Newcastle disease virus
Romanian Biotechnological Letters Vol. 14, No.4, 2009, pp. 4589-4596 Copyright 2008 Bucharest University Printed in Romania. All rights reserved Romanian Society of Biological Sciences ORIGINAL PAPER Predicting
More informationSupplementary Information
Coarse-Grained Molecular Dynamics Simulations of Photoswitchable Assembly and Disassembly Xiaoyan Zheng, Dong Wang,* Zhigang Shuai,* MOE Key Laboratory of Organic Optoelectronics and Molecular Engineering,
More informationBioInorganic Chemistry of Zinc Chemistry 2211a
BioInorganic Chemistry of Zinc Chemistry 2211a ZINC R17-iJ ZINC R17-iJ The role of zinc (an essential group 12 metal) 1. Zinc is everywhere in our environment 2. Zinc is a constituent of over 300 enzymes
More informationRSC Advances.
RSC Advances This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly
More informationSelf-association of α-chymotrypsin: Effect of amino acids
J. Biosci., Vol. 13, Number 3, September 1988, pp. 215 222. Printed in India. Self-association of α-chymotrypsin: Effect of amino acids T. RAMAKRISHNA and M. W. PANDIT* Centre for Cellular and Molecular
More informationProblem Set 1 September 10, 2009
September 10, 2009 This problem set consists of three problems designed to reinforce your knowledge of protein structure and energetics and to develop your skills at computationally analyzing protein sequences
More information33VASTVNGATSANNHGEPPS51PADARPR58
Pro-rich region Trans-membrane region 214 246 359 381 UL50 1 397 211SSRTAS216PPPPPR222 NLS CR1 CR2 CR3 CR4 UL53 1 376 11RERRS15ALRS19LLRKRRR25 33VASTVNGATSANNHGEPPS51PADARPR58 FIG S1. UL97 phosphorylation
More informationCaroline Elizabeth Lee. Department of Chemistry. Rhodes College. Memphis, Tennessee. Bachelor of Science degree with Honors in Chemistry
Quantum chemical analysis of ligand binding in the dopa decarboxylase active site and in silico design of novel ligands with improved active site binding affinity Caroline Elizabeth Lee Department of Chemistry
More informationSC/BIOL Biochemistry
SC/BIOL 2020.03 Biochemistry Midterm #1 Name: Student ID: Feb 7 th, 2013 Time: 1 hr and 15 min This test has multiple choice: 24 Marks. Fill in the blanks: 10 Marks Peptide structure: 6 Marks There are
More informationWiring diagram. A.-F. Miller, 2008, pg 1. Garrett & Grisham Fig
Wiring diagram 1 Garrett & Grisham Fig. 32.22 Gradients as signalling devices Nerve impulses propagated at 100 m/s Neuronal impulses are carried along axons as electrical signals: transient changes in
More informationSupplemental Data. Supplemental Text
Supplemental Data The magnitude of the light-induced conformational change in different rhodopsins correlates with their ability to activate G proteins. Hisao Tsukamoto, David L. Farrens, Mitsumasa Koyanagi
More informationMonocyte Innate Immune Response to Vitamin D
Monocyte Innate Immune Response to Vitamin D SIAM Life Science 2012 Session MS40 Signaling: Vitamin D in Monocytes and Receptor Clustering in Mast Cells Hewison and Adams laboratory UCLA-Orthopaedic Hospital
More informationChapter 10. Regulatory Strategy
Chapter 10 Regulatory Strategy Regulation of enzymatic activity: 1. Allosteric Control. Allosteric proteins have a regulatory site(s) and multiple functional sites Activity of proteins is regulated by
More information7.014 Problem Set 2 Solutions
7.014 Problem Set 2 Solutions Please print out this problem set and record your answers on the printed copy. Answers to this problem set are to be turned in at the box outside 68-120 by 11:45 Friday, February
More informationStudent number. University of Guelph Department of Chemistry and Biochemistry Structure and Function In Biochemistry
University of Guelph Department of Chemistry and Biochemistry 19356 Structure and Function In Biochemistry Midterm Test, March 3, 1998. Time allowed, 90 min. Answer questions 120 on the computer scoring
More informationFundamentals of Organic Chemistry CHEM 109 For Students of Health Colleges Credit hrs.: (2+1)
Fundamentals of Organic Chemistry CHEM 109 For Students of Health Colleges Credit hrs.: (2+1) King Saud University College of Science, Chemistry Department CHEM 109 CHAPTER 7. CARBOXYLIC ACIDS AND THEIR
More informationSUPPORTING INFORMATION. The Architecture of the TIR Domain Signalosome in the Toll-like Receptor-4. Signaling Pathway
SUPPORTING INFORMATION The Architecture of the TIR Domain Signalosome in the Toll-like Receptor-4 Signaling Pathway Emine Guven-Maiorov 1, Ozlem Keskin 1, Attila Gursoy 2*, Carter VanWaes 3, Zhong Chen
More informationHeat Shock Proteins in Targeted Cancer Chemotherapy
Heat Shock Proteins in Targeted Cancer Chemotherapy Aykut ÖZGÜR 1 and Yusuf TUTAR 2,* 1 Gaziosmanpaşa University, Faculty of Natural Sciences and Engineering, Department of Bioengineering, Tokat, Turkey
More information