DOCSLIB.ORG

Welcome to Week 2 Chapter 3 – Protein Structure 3.1 Intro To

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Welcome to Week 2 Chapter 3 – Protein Structure 3.1 Intro To Welcome to Week 2 Starting week two video Please watch the online video (1 minutes 24 seconds). OPTIONAL‐Please participate in the online discussion forum. Chapter 3 – Protein Structure Introduction to Chapter 3 Chapter 3 contains two subsections. Intro to Structure Part 1 Amino Acids, Primary Structure, and Secondary Structure Intro to Structure Part 2 Tertiary Structure, Quaternary Structure, and X‐Ray Crystallography At the conclusion of this chapter, you should understand how the ordering of individual amino acids in a protein can affect the localized and global folding and function of the entire protein. You should further have some appreciation of how x‐ray crystallographic data is used to determine the structure of proteins. OPTIONAL‐Please participate in the online discussion forum. 3.1 Intro to Structure Pt 1 Amino acids to secondary structure video Please watch the online video (8 minutes, 15 seconds). A condensed summary of this video can be found in the Video summary page. OPTIONAL‐Please participate in the online discussion forum. Working with Protein Data Bank entries Background: The structural information freely available in the Protein Data Bank is immense. It allows anyone to be able to study protein structure and function. Instructions: Use the tools in the PDB to examine the structures mentioned below and answer the assessment questions. Learning Goals: To learn how to manipulate proteins and identify their structural elements with the tools in the PDB. Please complete the online exercise. OPTIONAL‐Please participate in the online discussion forum. Finding PDB entry codes Background: Searching a specific entry in the Protein Data Bank requires one to know the corresponding PDB code. Instructions: Read the passage below concerning how PDB codes can be determined. Learning Goals: To learn how to find specific, useful information within the vast PDB database. The Protein Data Bank is only useful if one can find information of interest. As we work through this chapter, some students might wonder how to find other proteins. In the videos, I start with a PDB code. What if you do not already have a code? Searching the PDB requires one to have an idea of what is being sought. For the different examples in this course, I knew that I wanted to find proteins that are rich in one type of secondary structure. I performed an online search using terms like "proteins rich in alpha‐helices" and found a few names of proteins that seemed to match what I wanted. I then searched on those particular proteins within the PDB. Any single protein may have multiple entries in the PDB. I then looked through the different entries until I found a specific PDB entry that demonstrated the properties I want to highlight. Some websites on the internet include PDB codes. One example is SCOP: Structural Classification of Proteins, an extensive site that can be searched by a number of keywords that correspond to common traits of proteins. Most proteins in SCOP are linked to a PDB entry. OPTIONAL‐Please participate in the online discussion forum. 3.2 Intro to Structure Pt 2 Tertiary structure to X‐ray crystallography video Please watch the online video (7 minutes, 41 seconds). A condensed summary of this video can be found in the Video summary page. OPTIONAL‐Please participate in the online discussion forum. Validating protein structures Background: Most protein structures are determined based on x‐ray crystallographic data. The primary sequence of the protein is matched with the electron density map, and the individual amino acids are placed within the structure as closely as possible. After all the amino acids are positioned, the quality of the assigned structure can be measured with several tools. One of the most common tools is the Ramachandran plot. Instructions: Read the passage below about the use of Ramachandran plots to validate protein structural assignments. Learning Goal: To learn how Ramachandran plots graphically represents dihedral angles of individual amino acids to predict the validity of a proposed protein structure and folding. The Ramachandran plot is one of the primary methods for validating proposed protein structures based on x‐ray crystallographic data. The plot compares selected dihedral angles in each amino acid found within the proposed protein. The key dihedral angles for each amino acid are located along the backbone of the protein and are labeled φ (phi), ψ (psi), and ω (omega). To repeat, each amino acid residue contributes three rotatable bonds and three distinct dihedral angles to the backbone of a peptide chain. In theory, all dihedral angles can range in value from −180° to +180°. In practice, within a protein, the dihedral angles tend to fall in well‐defined ranges. Because of interactions between the nitrogen and carbonyl, ω is either 0 or 180°, typically 180°. φ has a value near ‐50° in an α‐helix and ranges between ‐50 and ‐160° in a β‐sheet. ψ also has a value near ‐50° in an α‐helix but ranges from +100 and +180° in a β‐sheet. When ψ is plotted against φ for each amino acid, most amino acids fall within tightly defined regions bounded by the angle ranges above and another small area for a specific subtype of α‐helix. Such a graph is called a Ramachandran plot, shown below. While keeping track of dihedral angles in a protein may seem complex, the Ramachandran plot makes the process very simple. Since most amino acid residues correspond to points that fall within predicted ranges, those amino acids can be ignored. The important ones are those that fall beyond the anticipated regions. Indeed, if a protein has over 5% of its amino acids as outliers, then the structure of that protein may be reasonably suspected as being improperly assigned. For this reason, the Ramachandran plot is a simple, visual tool for quickly checking the validity of an assigned protein structure. OPTIONAL‐Please participate in the online discussion forum. Evaluating Ramachandran plots Background: Ramachandran plots are a simple, visual tool for validating proposed protein structures. A website that allows users to generate Ramachandran plots from many PDB entries is the Ramachandran Server at Uppsala University in Sweden. Instructions: Compare the Ramachandran plots below to answer the questions. Learning Goals: To learn how to read and compare data from Ramachandran plots. Please complete the online exercise. OPTIONAL‐Please participate in the online discussion forum. Chapter 4 – Enzymes Introduction to Chapter 4 Chapter 4 contains three subsections. Michaelis‐Menten Kinetics Enzyme Inhibition Measuring Inhibition At the conclusion of this chapter, you should understand how enzyme kinetics data are presented graphically. You should also understand how different inhibitors affect enzymes, and how the inhibition is quantified. 4.1 Michaelis‐Menten Kinetics Theory of action video Please watch the online video (7 minutes, 8 seconds). A condensed summary of this video can be found in the Video summary page. OPTIONAL‐Please participate in the online discussion forum. Working with concentrations Background: Data in medicinal chemistry, including enzyme kinetics data, rely upon numbers with various concentration units. Being comfortable with interconverting different concentration units is a basic skill for one to have. Instructions: Read the passage below and use the information to answer the subsequent assessment questions. Learning Goal: To become comfortable working with the different types of units commonly encountered in medicinal chemistry. The goal of a drug discovery program is generally to find a molecule that binds a target protein at very low concentrations. As has been mentioned before (in Chapter 2), the binding is normally determined in a biochemical assay, often in the form of a dissociation equilibrium constant (KD). For a drug, the values for KD are very small, indicating the drug and target bind very tightly and do not readily dissociate. Ideal KD values are in the nanomolar (nM) range, but during development observed KD values are much higher. Hits in an early screen might have KD values in the micromolar (µM) range. The table below shows the concentrations regularly encountered in a drug discovery program. name description unit relation to molarity molar moles / liter M 1 millimolar millimoles / liter mM 10‐3 micromolar micromoles / liter µM 10‐6 nanomolar nanomoles / liter nM 10‐9 picomolar picomoles / liter pM 10‐12 Beyond the reporting of binding data (pharmacodynamics), the units in the table above are also found throughout pharmacokinetics, especially in reports of the concentration of drugs in blood. Please complete the online exercise. OPTIONAL‐Please participate in the online discussion forum. Graphing enzyme kinetics data Background: Interpreting enzyme kinetics data requires one to be able to graph the information. The previous unit contained a video which provided instructions on how to generate graphs from enzyme kinetics data as a saturation plot (Michaelis‐Menten equation) or in linear form (Lineweaver‐Burk equation). Instructions: Use the videos on graphing kinetics data in Google Docs, Apache OpenOffice, and Microsoft Excel to help you answer the assessment question below. Note that a sample calculation is available in the next component. If the question gives you trouble, consider peeking ahead to see one way to approach this problem. Learning Goals: To learn how to graph kinetics data and use the resulting plot to understand the activity of an enzyme. Linest in Google Docs spreadsheet video Please watch the online video (3 minutes 43 seconds). Linest in OpenOffice spreadsheet video Please watch the online video (4 minutes 9 seconds). Linest in Microsoft Excel video Please watch the online video (3 minutes 45 seconds). Please complete the online exercise. OPTIONAL‐Please participate in the online discussion forum. Sample calculation ‐ Lineweaver‐Burk plot Background: Lineweaver‐Burk plots depict 1/V vs. 1/[S]. These are very useful for determining the nature of enzyme‐substrate interactions.
Load more

Recommended publications
  • Biomolecules
    CHAPTER 3 Biomolecules 3.1 Carbohydrates In the previous chapter you have learnt about the cell and 3.2 Fatty Acids and its organelles. Each organelle has distinct structure and Lipids therefore performs different function. For example, cell membrane is made up of lipids and proteins. Cell wall is 3.3 Amino Acids made up of carbohydrates. Chromosomes are made up of 3.4 Protein Structure protein and nucleic acid, i.e., DNA and ribosomes are made 3.5 Nucleic Acids up of protein and nucleic acids, i.e., RNA. These ingredients of cellular organelles are also called macromolecules or biomolecules. There are four major types of biomolecules— carbohydrates, proteins, lipids and nucleic acids. Apart from being structural entities of the cell, these biomolecules play important functions in cellular processes. In this chapter you will study the structure and functions of these biomolecules. 3.1 CARBOHYDRATES Carbohydrates are one of the most abundant classes of biomolecules in nature and found widely distributed in all life forms. Chemically, they are aldehyde and ketone derivatives of the polyhydric alcohols. Major role of carbohydrates in living organisms is to function as a primary source of energy. These molecules also serve as energy stores, 2021-22 Chapter 3 Carbohydrade Final 30.018.2018.indd 50 11/14/2019 10:11:16 AM 51 BIOMOLECULES metabolic intermediates, and one of the major components of bacterial and plant cell wall. Also, these are part of DNA and RNA, which you will study later in this chapter. The cell walls of bacteria and plants are made up of polymers of carbohydrates.
    [Show full text]
  • Density Estimation for Protein Conformation Angles Using a Bivariate Von Mises Distribution and Bayesian Nonparametrics
    Density Estimation for Protein Conformation Angles Using a Bivariate von Mises Distribution and Bayesian Nonparametrics Kristin P. LENNOX, David B. DAHL, Marina VANNUCCI, and Jerry W. TSAI Interest in predicting protein backbone conformational angles has prompted the development of modeling and inference procedures for bivariate angular distributions. We present a Bayesian approach to density estimation for bivariate angular data that uses a Dirichlet process mixture model and a bivariate von Mises distribution. We derive the necessary full conditional distributions to fit the model, as well as the details for sampling from the posterior predictive distribution. We show how our density estimation method makes it possible to improve current approaches for protein structure prediction by comparing the performance of the so-called ‘‘whole’’ and ‘‘half’’ position dis- tributions. Current methods in the field are based on whole position distributions, as density estimation for the half positions requires techniques, such as ours, that can provide good estimates for small datasets. With our method we are able to demonstrate that half position data provides a better approximation for the distribution of conformational angles at a given sequence position, therefore providing increased efficiency and accuracy in structure prediction. KEY WORDS: Angular data; Density estimation; Dirichlet process mixture model; Torsion angles; von Mises distribution. 1. INTRODUCTION and Ohlson 2002; Lovell et al. 2003; Rother, Sapiro, and Pande 2008), but they behave poorly for these subdivided datasets. Computational structural genomics has emerged as a pow- This is unfortunate, because these subsets provide structure erful tool for better understanding protein structure and func- prediction that is more accurate, as it utilizes more specific tion using the wealth of data from ongoing genome projects.
    [Show full text]
  • Structure Validation Article
    14 STRUCTURAL QUALITY ASSURANCE Roman A. Laskowski The experimentally determined three-dimensional (3D) structures of proteins and nucleic acids represent the knowledge base from which so much understanding of biological processes has been derived over the last three decades of the twentieth cen- tury. Individual structures have provided explanations of specific biochemical functions and mechanisms, while comparisons of structures have given insights into general principles governing these complex molecules, the interactions they make, and their biological roles. The 3D structures form the foundation of structural bioinformatics; all structural analyses depend on them and would be impossible without them. Therefore, it is crucial to bear in mind two important truths about these structures, both of which result from the fact that they have been determined experimentally. The first is that the result of any experiment is merely a model that aims to give as good an explanation for the experimental data as possible. The term structure is commonly used, but you should realize that this should be correctly read as model. As such the model may be an accurate and meaningful representation of the molecule, or it may be a poor one. The quality of the data and the care with which the experiment has been performed will determine which it is. Independently performed experiments can arrive at very similar models of the same molecule; this suggests that both are accurate representations, that they are good models. The second important truth is that any experiment, however carefully performed, will have errors associated with it. These errors come in two distinct varieties: sys- tematic and random.
    [Show full text]
  • Chapter 13 Protein Structure Learning Objectives
    Chapter 13 Protein structure Learning objectives Upon completing this material you should be able to: ■ understand the principles of protein primary, secondary, tertiary, and quaternary structure; ■use the NCBI tool CN3D to view a protein structure; ■use the NCBI tool VAST to align two structures; ■explain the role of PDB including its purpose, contents, and tools; ■explain the role of structure annotation databases such as SCOP and CATH; and ■describe approaches to modeling the three-dimensional structure of proteins. Outline Overview of protein structure Principles of protein structure Protein Data Bank Protein structure prediction Intrinsically disordered proteins Protein structure and disease Overview: protein structure The three-dimensional structure of a protein determines its capacity to function. Christian Anfinsen and others denatured ribonuclease, observed rapid refolding, and demonstrated that the primary amino acid sequence determines its three-dimensional structure. We can study protein structure to understand problems such as the consequence of disease-causing mutations; the properties of ligand-binding sites; and the functions of homologs. Outline Overview of protein structure Principles of protein structure Protein Data Bank Protein structure prediction Intrinsically disordered proteins Protein structure and disease Protein primary and secondary structure Results from three secondary structure programs are shown, with their consensus. h: alpha helix; c: random coil; e: extended strand Protein tertiary and quaternary structure Quarternary structure: the four subunits of hemoglobin are shown (with an α 2β2 composition and one beta globin chain high- lighted) as well as four noncovalently attached heme groups. The peptide bond; phi and psi angles The peptide bond; phi and psi angles in DeepView Protein secondary structure Protein secondary structure is determined by the amino acid side chains.
    [Show full text]
  • Prediction of Amino Acid Side Chain Conformation Using a Deep Neural
    Prediction of amino acid side chain conformation using a deep neural network Ke Liu 1, Xiangyan Sun3, Jun Ma3, Zhenyu Zhou3, Qilin Dong4, Shengwen Peng3, Junqiu Wu3, Suocheng Tan3, Günter Blobel2, and Jie Fan1, Corresponding author details: Jie Fan, Accutar Biotechnology, 760 Parkside Ave, Room 213 Brooklyn, NY 11226, USA. [email protected] 1. Accutar Biotechnology, 760 parkside Ave, Room 213, Brooklyn, NY 11226, USA. 2. Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA 3. Accutar Biotechnology (Shanghai) Room 307, No. 6 Building, 898 Halei Rd, Shanghai, China 4. Fudan University 220 Handan Rd, Shanghai, China Summary: A deep neural network based architecture was constructed to predict amino acid side chain conformation with unprecedented accuracy. Amino acid side chain conformation prediction is essential for protein homology modeling and protein design. Current widely-adopted methods use physics-based energy functions to evaluate side chain conformation. Here, using a deep neural network architecture without physics-based assumptions, we have demonstrated that side chain conformation prediction accuracy can be improved by more than 25%, especially for aromatic residues compared with current standard methods. More strikingly, the prediction method presented here is robust enough to identify individual conformational outliers from high resolution structures in a protein data bank without providing its structural factors. We envisage that our amino acid side chain predictor could be used as a quality check step for future protein structure model validation and many other potential applications such as side chain assignment in Cryo-electron microscopy, crystallography model auto-building, protein folding and small molecule ligand docking.
    [Show full text]
  • NIH Public Access Author Manuscript Proteins
    NIH Public Access Author Manuscript Proteins. Author manuscript; available in PMC 2009 May 11. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Proteins. 2008 June ; 71(4): 1637±1646. doi:10.1002/prot.21845. Using Quantum Mechanics to Improve Estimates of Amino Acid Side Chain Rotamer Energies P. Douglas Renfrew, Glenn Butterfoss, and Brian Kuhlman Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, Email: [email protected] Abstract Amino acid side chains adopt a discrete set of favorable conformations typically referred to as rotamers. The relative energies of rotamers partially determine which side chain conformations are more often observed in protein structures and accurate estimates of these energies are important for predicting protein structure and designing new proteins. Protein modelers typically calculate side chain rotamer energies by using molecular mechanics (MM) potentials or by converting rotamer probabilities from the protein database (PDB) into relative free energies. One limitation of the knowledge-based energies is that rotamer preferences observed in the PDB can reflect internal side chain energies as well as longer-range interactions with the rest of the protein. Here, we test an alternative approach for calculating rotamer energies. We use three different quantum mechanics (QM) methods (second order Moller-Plesset (MP2), density functional theory (DFT) energy calculation using the B3LYP functional, and Hartree-Fock) to calculate the energy of amino acid rotamers in a dipeptide model system, and then use these pre-calculated values in side chain placement simulations. Energies were calculated for over 35,000 different conformations of leucine, isoleucine and valine dipeptides with backbone torsion angles from the helical and strand regions of the Ramachandran plot.
    [Show full text]
  • Theoretical Protein Structure Prediction of Glucagon-Like Peptide 2 Receptor Using Homology Modelling
    J. Chosun Natural Sci. Vol. 10, No. 3 (2017) pp. 119 − 124 https://doi.org/10.13160/ricns.2017.10.3.119 Theoretical Protein Structure Prediction of Glucagon-like Peptide 2 Receptor Using Homology Modelling Santhosh Kumar Nagarajan1,2 and Thirumurthy Madhavan2† Abstract Glucagon-like peptide 2 receptor, a GPCR, binds with the glucagon-like peptide, GLP-2 and regulates various metabolic functions in the gastrointestinal tract. It plays an important role in the nutrient homeostasis related to nutrient assimilation by regulating mucosal epithelium. GLP-2 receptor affects the cellular response to external injury, by controlling the intestinal crypt cell proliferation. As they are therapeutically attractive towards diseases related with the gastrointestinal tract, it becomes essential to analyse their structural features to study the pathophysiology of the diseases. As the three dimensional structure of the protein is not available, in this study, we have performed the homology modelling of the receptor based on single- and multiple template modeling. The models were subjected to model validation and a reliable model based on the validation statistics was identified. The predicted model could be useful in studying the structural features of GLP-2 receptor and their role in various diseases related to them. Keywords: GLP2 Receptor, GPCR, GLP2, Homology Modelling. 1. Introduction nutrient homeostasis proximal to nutrient assimilation by controlling the stasis of mucosal epithelium. The sig- Glucagon and glucagon like peptides (GLPs) are nalling via GLP-2 receptor regulates the intestinal crypt secreted in the pancreas, gut, CNS and PNS and control cell proliferation, directly affecting the cellular response various metabolic functions[1].
    [Show full text]
  • Protein Structure Prediction and Potential Energy Landscape Analysis Using Continuous Global Minimization
    Protein Structure Prediction and Potential Energy Landscape Analysis using Continuous Global Minimization KEN A. DILL Departmentof Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, CA 94118 <[email protected]~edu~ ANDREW T. PHILLIPS ComputerScience Department, United StatesNaval Academy,Annapolis, MD 21402 <[email protected]> J. BEN ROSEN Computer Science and Engineering Department, University of California at San Diego, San Diego, CA 92093 <[email protected]> INTRODUCTION form of energy minimization technique, such as simu- lated annealing and genetic algorithms, rather than the Proteins require specific three-dimensional conforma- computationally more efficient continuous minimiza- tions to function properly. These “native” conforma- tion techniques. Each such method correctly predicts a tions result primarily from intramolecular interactions few protein structures, but missesmany others, and the between the atoms in the macromolecule, and also process is both slow and limited to structures of rela- intermolecular interactions between the macromole- tively small size. cule and the surrounding solvent. Although the folding The purpose of this paper is to show how one can process can be quite complex, the instructions guiding apply more efficient continuous minimization tech- this process are specified by the one-dimensional pri- niques to the energy minimization problem by using mary sequenceof the protein or nucleic acid: external an accurate continuous approximation to the discrete factors, such as helper (chaperone) proteins, present at information provided for known protein structures. In the time of folding have no effect on the final state of addition, we will show how the results of one particu- the protein. Many denatured proteins spontaneously lar computational method for protein structure predic- refold into functional conformations once denaturing tion (the CGU algorithm), which is based on this conditions are removed.
    [Show full text]
  • Three Dimensional Structure Modeling and Ramachandran Plot Analysis of Autographa Californica Nucleopolyhdro Viral Protein
    Gopukumar et al (2020): Analysis of nucleopolyhedro viral protein March 2020 Vol. 23 Issue S6 Three dimensional structure modeling and ramachandran plot analysis of autographa californica nucleopolyhdro viral protein S.T. Gopukumar1*, Sreeya G. Nair2, R. Radha2, N.V. Sugathan3, Anooj E. S4, Lekshmi Gangadhar4 1Department of Medical Research, Sarada Krishna Homoeopathic Medical College, Kulasekharam. TN, India 2Department of Zoology, Sree Ayyappa College for Women, Chunkankadai, Nagercoil, TN, India 3Department of Practice of Medicine, Sarada Krishna Homoeopathic Medical College, Kulasekharam. TN, India 4Xcellogen Biotech India Pvt Ltd, Nagercoil, Tamilnadu, India *Corresponding Author E-mail: [email protected] (Gopukuma) ABSTRACT: Background: Autographa Californica’s nucleopolyhedro is a viral protein found in baciloviridae. It is made of double stranded DNA genome. They viral protein easily infects this insect and affects the expression system. Method: The main aim of this work is to predict various viral proteins (Autographa Californica nucleopolyhedro). FASTA sequences are retrived from NCBI (National Center for Biotechnology Information) database. Then Basic Local Alignment Search Tool (BLAST) used to find regions of similarity in different sequences. The homology modeling was done in swiss model. The template model also constructed. Results: Comparative modeling of this program to predict the protein sequence identity is 46.83%.The template protein e value is 110 and they chain A having identify 100% similarity maximum score 320.Further the protein structure was validated in Ramachandran plot. Conclusion: From Ramachandran plot analysis it was found that the portions of residues falling into the favored regions was 98%.The predicted 3D model further characterized and analyzed using other techniques.
    [Show full text]
  • Molecular Modeling 2021
    Molecular Modeling 2021 A course about proteins protein conformation protein shape Protein energy protein interactions protein dynamics protein drug interactions Administrative • Course website: on Blackboard learn: https://lms.rpi.edu/ • Office hour: 4 – 5 PM Wednesdays, on webex • Grading policy – Assignment and quiz (30 % total) – midterm (20%) – final (20%) – Presentation (20%) – Class participation (answering questions in class) and attendance (10%) • Questions ALWAYS welcome! Syllabus Installing MOE • Download MOE to your personal computer using file on RPI box https://rpi.box.com/s/ mdjcw69wffo5roe5p7nse4n16wznf97u !! If your RPI box account is not set up, use this link to set it up: https://itssc.rpi.edu/hc/en-us/articles/ 360004829931-Requesting-a-Box-RPI-Account • Copy the license file (license.dat in the box directory) into the installed MOE local directory • To run MOE, you need to access the license server located on RPI campus: got to have VPN running! – Install “cisco anyconnec”t: https://itssc.rpi.edu/hc/en-us/ articles/360008783172-VPN-Installation-and-Connection Instructor • Chunyu Wang • Associate Professor of Biological Sciences • Expert in NMR, protein structure, Alzheimer's disease, Inteins and Hedgehog autoprocessing • Hobbies: photography, astronomy, astrophotography, tennis, bridge, gardening, swimming etc. NMR structure of Pab PolII intein: Hint fold Cover of Nov.4th 2011 Issue of JBC Hint = Hedgehog Intein domain/fold Du et.al. J. Biol. Chem., 2011, 286, 38638-38648. 6 What are Aβ, Αβ40 and Αβ42 ? Aβ42 Aβ40 Major component of the amyloid plaque Aβ40 and Aβ42 are major species of Aβ Aβ42 aggregates faster and is more toxic than Aβ40 In familial Alzheimer’s disease (FAD), Aβ42/Aβ40 ↑ Aβ40 Aβ42 .
    [Show full text]
  • Bioinformatics for Molecular Biology Structural Bioinformatics Tools, Predictors, and 3D Modeling – Structural Biology Review
    Bioinformatics for molecular biology Structural bioinformatics tools, predictors, and 3D modeling – Structural Biology Review Dr Jon K. Lærdahl, Research Scientist Department of Microbiology, Oslo University Hospital - Rikshospitalet & Bioinformatics Core Facility/CLS initiative, University of Oslo E-mail: [email protected] Phone: +47 22844784 Group: Torbjørn Rognes (http://www.ous-research.no/rognes) CF: Bioinformatics services (http://core.rr-research.no/bioinformatics) CLS: Bioinformatics education (http://www.mn.uio.no/ifi/english/research/networks/clsi) Main research area: Structural and Applied Bioinformatics Jon K. Lærdahl, Structural Bioinformatics Now: Overview • Protein Structure Review – Amino acids, polypeptides, secondary structure elements, visualization, structure determination by X-ray crystallography and NMR methods, PDB Later… • Structure comparison and classification (CASP & SCOP) • Predictors • 3D structure modeling – Ab initio – Threading/fold recognition – Homology modeling • Practical exercises – PyMOL & visualization • Practical Exercises – Homology modeling of influenza neuraminidase (Tamiflu resistance?) – Other homology modeling – Threading – Your own project? Stop me and ask questions!! Jon K. Lærdahl, Amino acids – the building blocks Structural Bioinformatics Proteins are built from 20 naturally occurring amino of proteins acids. They have an amino (-NH2) and acidic The side chain group (R) determines the properties of the (-COOH) functional group amino acid Side chain Carboxyl group Amino Zwitterionic form
    [Show full text]
  • Ramachandran Plot, Helices, Turns and Sheets)
    E-content M.Sc. Zoology (Semester II) CC7- Biochemistry Unit: 3.3 Peptide conformations (Ramachandran plot, helices, turns and sheets) Dr Gajendra Kumar Azad Assistant Professor Post Graduate Department of Zoology Patna University, Patna Email: [email protected] 1 The peptide bond conformations The primary structure of a protein is defined as the sequence of amino acids in a polypeptide chain. This sequence determines the shape of the protein which depends on the spatial limitations of the atoms present in the protein, the chemical properties of the component amino acid residues, and the protein's environment. The peptide bonds that link amino acid residues in a polypeptide are formed in a condensation reaction between the carboxyl group of one amino acid and the basic amino group of another amino acid. In the context of a peptide, the CO–NH group is referred to as the peptide bond. Linus Pauling, in the 1930s, used X-ray diffraction to examine the nature of the peptide bond formed between two amino acids. He reported that the peptide group (CO–NH) has a rigid planar structure. Figure 1: Peptide bond joins two amino acids 2 Peptide bond have partial double bond properties The rigid planer structure of peptide bond is due to interactions between electrons of the double bond of the carbonyl group and those of the C–N bond such that the latter acquires partial (about 40%) double-bond properties. This effect is an example of resonance which can be thought of as a sharing of electrons between bonds. The partial double bond character of C–N in the peptide group means that this bond is shorter than would be predicted for a C–N single bond, whilst the C=O bond, having a partial single bond character due to resonance, is longer than would be predicted for a C=O double bond.
    [Show full text]