Matthew K. Oki Individual Journal 8

Preparation for Week 9 Journal Club

Biological Terms

1. glycoprotein
   • "One of a group of compounds consisting of a protein combined with a carbohydrate (such as galactose or mannose). Examples of glycoproteins are certain enzymes, hormones, and antigens."
   • http://www.oxfordreference.com/view/10.1093/oi/authority.20110803095856565
2. Simulated Annealing Algorithm
   • "A technique used in data mining to select an optimal set of data from a large space of solutions. The term comes from the fact that the techniques uses a process similar to that found when metals are cooled slowly."
   • http://www.oxfordreference.com/view/10.1093/oi/authority.20110803100507504
3. Chemokine co-receptors
   • "Any one of a group of small proteins that guide leucocytes to sites of infection and are vital for immune function. They fall into two main classes, CC chemokines and CXC chemokines; receptors (denoted R) are named after the class that bind to them, and subtypes of each class are indicated by numbers (e.g. CCR5)."
   • http://www.oxfordreference.com/view/10.1093/oi/authority.20110803095605484
4. Immunochemical
   • "any specific immunological reagent that consists of or incorporates an antigen or an antibody, especially one of commerce."
   • http://www.oxfordreference.com/view/10.1093/oi/authority.20110803095958733
5. X-ray crystallography
   • "The study of the geometric forms of crystals by X‐ray diffraction."
   • http://www.oxfordreference.com/view/10.1093/oi/authority.20110803125218110
6. Transient
   • "Lasting only for a short period of time."
   • http://www.oxfordreference.com/view/10.1093/acref/9780199641666.001.0001/acref-9780199641666-e-8368?rskey=tPcmHs&result=2
7. Dihedrals
   • "An angle formed by the intersection of two planes (e.g. two faces of a polyhedron). The dihedral angle is the angle formed by taking a point on the line of intersection and drawing two lines from this point, one in each plane, perpendicular to the line of intersection."
   • http://www.oxfordreference.com/view/10.1093/oi/authority.20110803095718396
8. Immunogenic
   • "Capable of stimulating an immune response."
   • http://www.oxfordreference.com/view/10.1093/acref/9780199766444.001.0001/acref-9780199766444-e-3321?rskey=tZbOkd&result=1
9. Collating
   • "An ordering of the internal character set, used in alphabetic and alphanumeric sorting."
   • http://www.oxfordreference.com/search?q=collating%20sequence
10. glycosylated
    • "The process of adding sugar units such as in the addition of glycan chains to proteins. An occurrence where a carbohydrate is added to a protein molecule, which can occur in the golgi apparatus."
    • http://www.biology-online.org/dictionary/Glycosylation

Outline

Introduction

• HIV-1 enters the host cell through interaction with CD4 cell surface receptors and a chemokine co-receptor.
• The V3 loop is a highly variable portion of HIV-1 that is the target for antiviral drugs.
  • The variability prevents antibodies from affecting any other isolates.
  • However, some of the amino acid positions in the N-and C- terminals are conserved.
    • They are most likely conserved to preserve the conformational status of the virus
• The 3D structure of HIV-1 must be found to implement drugs that can inflict the conserved portion of the virus.
• HIV-1 Subtype B dominates North and South American and is given preference in research, but computer-made structures are helping close the gap for subtype A, which prevails in Central Africa and Eastern Europe.
• 5 major steps were completed in this study:
  • The low-energy confirmation for the V3 loop of HIV-1 subtype A was generated
  • The secondary structures of V3 were characterized in the built conformations
  • NMR spectroscopy and X-rays were used to reveal the motif structures of the V3 loop
  • The molecular dynamics trajectory was found to investigate the conformational features in more depth
  • Finally, molecular docking was used to see if the V3 loop kept in touch with the ligands

Methods

• Modeling of 3D V3 Structures
  • Comparative modeling methods were used on the structures found from NMR spectroscopy and X-ray studies
  • The MODELLAR package was used in comparative modeling of 100 models for each template.
  • The subsets with the 10 best models were selected for energy optimization and final refinement
  • The AMBER and TINKER software were used to find energy optiminations
• Identification of Secondary V3 Structures
  • The phi and psi bond values of each amino acid were derived from the simulated models
  • Classical and non-standard B-turns were found by using classifications created by previous authors.
• Comparison of 3D V3 Structures
  • Root-mean-square deviations were calculated for the entire V3 structure and the individual fragments of 4 to 9 residues
• Molecular Dynamics Computations
  • GROMACS software was used for molecular dynamics computations
• Molecular Docking Simulations
  • These simulations were presented in the Hex 4.5 program in order to display possible docking areas for pairs of protein and DNA

Questions

1. What is the main result (message) presented in this paper?
2. What is the importance or significance of this work?
3. What were the limitations in previous studies that led them to perform this work?
4. What were the methods used in the study?
5. Briefly state the result shown in each of the figures and tables.
6. How do the results of this study compare to the results of previous studies.

Acknowledgements

• I would like to thank my partners, Mia Huddleston, Zachary T. Goldstein, and Welliam P. Fuchs, for the assistance on this weeks project both in the understanding of our paper in class and completion of the powerpoint outside of class
• I would also like to thank Kam D. Dahlquist, Ph.D. for providing the instructions and information for this assignment both in class and on this document: BIOL368/F16:Week 8.
• Even though I worked with the people noted above, this individual journal entry was completed by me and not copied from another source.
• Matthew K. Oki 17:44, 19 October 2016 (EDT):

References

1. BIOL368/F16:Week 8
2. Andrianov, A. M., & Anishchenko, I. V. (2009). Computational model of the HIV-1 subtype A V3 loop: Study on the conformational mobility for structure-based anti-AIDS drug design. Journal of Biomolecular Structure and Dynamics, 27(2), 179-193. DOI: 10.1080/07391102.2009.10507308

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