Analysis of a drug bound to a G protein-coupled receptor

Analysis of a drug bound to a G protein-coupled receptor


G protein-coupled receptors (GPCRs) are the largest family of integral membrane proteins inthehumangenomeareimportantdrugtargets.

Within the human genome there are coded over 1000 GPCRs and compounds that act at these targets comprise more than 50% of the current market for human drugs. Understanding how GPCRs function and bind to drugs is of importance to researchers in the search for new drugs. A better understanding will facilitate design and help to avoid compounds with undesirable side effects.

This practical exercise will provide a general overview of the GPCR protein and will explore the design of a compound within the active site using a GPCR structure with an agonist.


To investigate GPCR protein structure and the amino acids involved in the binding of an agonist using the 2-adrenergic receptor as an example. To design novel ligands to improve potency and selectivity.

The Report:Please answer the questions in the exercise in your report. No Aims, Methods, etc. are required. All images should include a figure legend.




Extracellular loops

Intracellular loops


  • GPCRs are proteins that transfer signals from outside the cell into the cell interior.
  • GPCRs are embedded in the cell membrane with regions (loops) exposed to inside and outside of the cell.
  • The protein passes through the membrane 7 times (hence 7TM). There is an eighth helix that is located inside the cell (and does not pass through the membrane).
  • The transmembranesectionof all GPCRs are very similar but the extracellular and intracellular loops can vary greatly.


GPCRs which interact with a huge variety of different neurotransmitters or hormones which can be classified in the following manner:

  • Monoamines(e.g. adrenaline, dopamine, 5HT)
  • Nucleotides
  • Lipids
  • Neuropeptides (e.g. leu and met-enkephalin), peptide hormones and protein hormones
  • Glycoprotein hormones
  • Glutamate
  • Calcium ions
  • The binding sites for their various ligands differs between the classes.
  • The binding site for monoamines, nucleotides and lipids is deep within the structure between the transmembrane helices.
  • Upon binding of the chemical messenger to the GPCR the G protein then interacts with the receptor-ligand complex. The G protein then carries the ‘message’ to the next target in the signalling cascade.

Crystal structure of an opioid bound to the mu opioid receptor

Information about the crystal structure is available from the Protein Data Bank (PDB)

Question 1.

GotothePDBdatabasesiteandsearchforentry4DKL.This is the structure of the mu opioid receptor bound to the ligand, β-funaltrexamine, which is an analogue of buprenorphine.

Three lipid molecules and one polyethylene glycol molecule are also present in the crystalstructure.

The original paper that discusses the crystal structure is available here: (or on Moodle). The supplementary information from the paper will also help answer this question (on Moodle also).

Find the structure of the β-funaltrexamine. Using a diagram, show how the ligand has made a covalent bond with the receptor. The formation of the covalent bond permanently attaches the ligand to the receptor, which assists with protein crystallisation for X-ray crystallography.


Obtain the 4DKL protein crystal structure of the mu opioid receptor to the irreversible morphine-like antagonist β-funaltrexamine (β-FNA).

In the PyMOL> command box type:

fetch 4DKL

oruse the command FileGet PDB (if it exists).

Pymol mouse commands:

Left mouse: rotate or select Right mouse: scale

Middle mouse (wheel): click to centre structure Pymol display matrix:

Structures can be turned on and off by clicking on the grey section

A = action S = show H= hide

L= label

C= colour


Show the structure in cartoon format (other representations are possible too) AllHideeverything


Show the small (organic) molecules in the crystal structure AllShoworganicsticks

Note that the protein is made up of three domains. One of these is the 7-transmembrane (7TM) region, the focus of our interest, while the remaining sections were used to help examine the agonist state of the receptor.

The crystal structure contains genetically engineered domains that are not part of the GPCR. These were used to help crystallise the protein.

Rotate the structure and identify the 7TM region. To help clearly visualize the 7TM domain we will remove the other domains.

In the PyMOL> command box type:

select xxx, resi 1000-1200 select yyy, resname so4

select zzz, resname 1pe [ don’t forget the comma ]

Delete the bits we don’t want

xxxActionremove atoms yyyActionremove atoms zzzActionremove atoms

Colour the protein chains as a rainbow (N-terminus blue, C-terminus red) AllColourspectrumrainbow

We now have the structure with the key 7TM domain (and some substructures that interact with the protein). Take some time to inspect the 7TM structure. Can you identify helices 1- 8?

Question 2.

Maketwodiagrams: [ use print screen or use Draw/Ray in top right corner ]

  1. Onefromtheviewoflookingacrossthemembrane.
  2. Onelookingdownontopofthe7TMdomain(fromtheoutsideofthecell)

Using your diagrams. a) briefly describe the structure of the protein b) identify the boundligandandthe3boundlipidmolecules.


In the crystal structure, there is a cholesterol molecule (residue name CLR, residue number 614) that we will explore further.


The first step will involve hiding everything.

4DKL  Hide everything

To display the glycerol ester and surrounding amino acids type the following into the command box:

In the PyMOL> command box type:

select clr, resi 614 expand 6.0

Show the atoms

clrShowsticks Colour the atoms by element

AllColourby element where C is green.

Colour the lipid a different colour Click on the lipid to select it.

SeleColourby element where C is aqua.

Label residues

clrlabelresidues Centre the structure


Question 3.




To look at this more closely we need to display the ligand (β-funaltrexamine, BF0) and residues close to this compound. (Note last character is zero).

First hide everything

All  Hide  everything

All  Label clear [ might be necessary ] Display β-FNA and surrounding amino acids define a selection

In the PyMOL> command box type:

select bf0, resn bf0 expand 6

Label residue names

bf0Labelresidues bf0showsticks

Colour the ligand a different colour from the other residues Select and centre the ligand

seleColourby element(colour scheme) sele->Action->center



Wizard (menu)Measurementdistance

Click on atoms to measure distance. Choose Done when finished. [ if you do not have a Wizard menu:

In the PyMOL> command box type:

wizard distance



Identify the colvalent linkage that has been created between the ligand and protein.

An aspartic acid residue (Asp, one letter code D) makes strong interactions with the ligand.

Question 4.

Whatisthenumberofthisresidue?Whattypeofinteraction(s)doestheligandmakewiththisresidue? (Note that hydrogen atoms are not shown in the crystal structure). How does thisresiduecontributetothemuopioidpharmacophore?(seelectureNotes).

Question 5.





Finally, we wish to design a new compound using β-FNA as our template. The compound β- FNA is derived from morphine, being substituted at the 6 position and having the double bond in the C ring reduced.






HO 6

One way to improve affinity (and possibly selectivity) of our template for the receptor is to design a compound which makes an additional interaction with the receptor. To do this we need to identify a residue adjacent to the ligand that might be able to provide an additional interaction.

Question 6.

Design ligands modifying the 6-position of β-FNA and that make new interactions with the receptor. Explain why you think they would improve ligand binding.

Universal Assignment (June 7, 2023) Analysis of a drug bound to a G protein-coupled receptor. Retrieved from
"Analysis of a drug bound to a G protein-coupled receptor." Universal Assignment - June 7, 2023,
Universal Assignment May 28, 2022 Analysis of a drug bound to a G protein-coupled receptor., viewed June 7, 2023,<>
Universal Assignment - Analysis of a drug bound to a G protein-coupled receptor. [Internet]. [Accessed June 7, 2023]. Available from:
"Analysis of a drug bound to a G protein-coupled receptor." Universal Assignment - Accessed June 7, 2023.
"Analysis of a drug bound to a G protein-coupled receptor." Universal Assignment [Online]. Available: [Accessed: June 7, 2023]

Please note along with our service, we will provide you with the following deliverables:

Please do not hesitate to put forward any queries regarding the service provision.

We look forward to having you on board with us.

Get 90%* Discount on Assignment Help

Most Frequent Questions & Answers

Universal Assignment Services is the best place to get help in your all kind of assignment help. We have 172+ experts available, who can help you to get HD+ grades. We also provide Free Plag report, Free Revisions,Best Price in the industry guaranteed.

We provide all kinds of assignmednt help, Report writing, Essay Writing, Dissertations, Thesis writing, Research Proposal, Research Report, Home work help, Question Answers help, Case studies, mathematical and Statistical tasks, Website development, Android application, Resume/CV writing, SOP(Statement of Purpose) Writing, Blog/Article, Poster making and so on.

We are available round the clock, 24X7, 365 days. You can appach us to our Whatsapp number +1 (613)778 8542 or email to . We provide Free revision policy, if you need and revisions to be done on the task, we will do the same for you as soon as possible.

We provide services mainly to all major institutes and Universities in Australia, Canada, China, Malaysia, India, South Africa, New Zealand, Singapore, the United Arab Emirates, the United Kingdom, and the United States.

We provide lucrative discounts from 28% to 70% as per the wordcount, Technicality, Deadline and the number of your previous assignments done with us.

After your assignment request our team will check and update you the best suitable service for you alongwith the charges for the task. After confirmation and payment team will start the work and provide the task as per the deadline.

Yes, we will provide Plagirism free task and a free turnitin report along with the task without any extra cost.

No, if the main requirement is same, you don’t have to pay any additional amount. But it there is a additional requirement, then you have to pay the balance amount in order to get the revised solution.

The Fees are as minimum as $10 per page(1 page=250 words) and in case of a big task, we provide huge discounts.

We accept all the major Credit and Debit Cards for the payment. We do accept Paypal also.

Popular Assignments

BAFI 3257 – Corporate Financial Management

School of Economics, Finance and Marketing Master of Finance BAFI 3257 – Corporate Financial Management ASSESSMENT TASK 3 – INDIVIDUAL ASSIGNMENT Semester 1 – 2021 Marks Due Date Submission Instructions Objective In this assignment, you are required to apply techniques and concepts acquired in this course to analyse and provide

Read More »

MMP742 – Investment Valuation

MMP742 – Investment Valuation Trimester 1, 2021 Assessment Task 2 DUE DATE AND TIME:                        Week 10, 17/05/2021, 8PM (AEST) PERCENTAGE OF FINAL GRADE:        25% WORD COUNT:                                   2,500 words Learning Outcome Details Unit Learning Outcome (ULO) Graduate Learning Outcome (GLO) ULO 1: Collect, evaluate and interpret market data relevant to property

Read More »

Initial Instructions: Research Report

General Information For this assignment, the class will participate in a simple research project which you will write up as a research report with the following sections: Abstract, Introduction, Method, Results, Discussion and References. In order to successfully complete this assignment, you will need to I encourage you to work

Read More »

LST3LPC Policy Proposal

Due: Tuesday October 26 (11:59pm) Size: 1500 words Worth: 40% Submission: Turnitin Description Students are required to produce a policy proposal, including the discussion of a social issue, policy options and recommendations. To support students to complete this task comprehensively and in accordance with expectations for policy proposals produced outside

Read More »

HLT54115 Diploma of Nursing

Assessment 2: Literature Review- Evidence-Based Practice HLT54115 Diploma of Nursing CHCPOL003 Research and apply evidence to practice Instructions for Student Instructions Select one of the topics below and undertake a literature review using evidence-based Practice (EBP).   Topics The impacts of effective hand hygiene practices in nursing.Improvements in nursing interventions

Read More »

Assessment 2 – Narrated Presentation

Assessment 2 – Narrated Presentation Assessment Type Narrated Presentation of an Educational Resource Description: Teaching and Learning Outline.  In this assessment item you are required to: 1. Topic is: Blood Glucose level management and subcutaneous insulin application for patients with type 2 diabetes. 2. Conceptualise an educational resource that will

Read More »


FOOD PANDA Question 2 – Delivery performance measure Delivery Performance is the level at which an organization’s provision of products and services meets the criteria anticipated by its consumers. To achieve maximum client happiness, service providers must focus on quality. The top 2 approaches performance measure to evaluate their food

Read More »

BUSN3003 Exam – Session 2, 2021

BUSN3003 Exam – Session 2, 2021 Instructions: Please save this document onto your computer. Type your answers into the document, saving the document as you go – you don’t want to lose any answers! Once complete, upload the final document via the Turnitin Exam Submission Link on the Blackboard site

Read More »

Hospitality Services Management

Hospitality Services Management Group members: each doing 7 marks worth Chloe Kate Tori Gideon Assessment 2 Group Task – (using a Wiki) A Group Task, using a Wiki, to create a new service organisation Related Topics: 3, 4, 5 & 6. You have been assigned to a group drawn from

Read More »

Development and Construction – Assignment 3

Development and Construction – Assignment 3 Marking Guide This is a guide to help you with the structuring of your report and highlighting what specific information should be included in your report. You should use information from your previous assignments, including designs and the feasibility study, as the basis for

Read More »

Case Analysis Sarita

Sarita due Sunday 12 September 2021 2500 words ± 10% You will be marked against the criteria in the marking rubric for Case analysis. Theme  5 Stress response in health and illness and theme 6 Immunology concepts Weighting: 50% referenced using APA style. • ll written assessments are to be

Read More »

Assignment 1: Argumentative Essay

Assignment 1: Argumentative Essay Topic Healthcare professionals have an ethical responsibility to always advocate for the introduction of new treatments and technologies into healthcare. Instructions In relation to your selected topic: • Consider the application of the bioethical principles. • Consider the application of ethical theories and other ethical concepts.

Read More »

Healthcare Ethics Argumentative essay

ASSESSMENT INFORMATION   Assessment Title   Argumentative essay     Purpose The purpose of this assessment is for students to demonstrate the capacity to develop an ethical argument/s based around the four bio-ethical principles: autonomy, justice, beneficence, and non-maleficence. Students will use their chosen topic to develop a sound ethical

Read More »

Marking Guide for Assessment 1 Part B: Reflection

Marking Guide for Assessment 1 Part B: Reflection Reflection (Total of 30 marks) – Due 31st October 2021 Reflect on the desirable qualities of counselling and how these qualities shape your approach and values to counselling and/or developing a therapeutic professional relationship. Reflect on your PART A reflection and consider

Read More »

Critical Reflection scenario-based essay

Purpose: The purpose of this assessment is to deepen student’s understanding of the characteristics of leadership styles and the dynamic relationship of leadership with workplace communication and culture. Aim: This assessment provides the student the opportunity to apply and evaluate leadership styles in a scenario involving making changes to improve workplace

Read More »

MBA621 Healthcare Systems

Assessment 2 Information Subject Code: MBA621 Subject Name: Assessment Title: Assessment Type: Length: Case Study Slide Deck Individual PowerPoint presentation slides with notes 2000 words (+/- 10% allowable range) 20 slides with 100 words per slide Weighting: 35% Total Marks: Submission: 100 Online Due Date: Weeks 7 Your task Develop

Read More »

MATH7017: Probabilistic Models and Inference

MATH7017: Probabilistic Models and Inference, Project 2023                    (total: 40 points) Conditional Generation with Variational Autoencoders and Generative Adversarial Networks Overview In this project, you will work with Variational Autoencoders (VAEs) and Generative Adversarial Networks (GANs). You will build and train conditional versions of these models to generate MNIST digits given

Read More »

Surveying Plan Assignment Help

Submission Component and Marks Awarded Marks   PLAN:     Find Scale of plan and explain 4   9 Bearing and Distances of three lines 3 Plan Presentation 2 HORIZONTAL ALIGNMENT     Deflection Angles 4   18 Curve Elements 4 Chainages along the Road 10 VERTICAL ALIGNMENT:    

Read More »

NURBN3034 Assessment Task

NURBN3034 Assessment Task 1a Global Health Issues Group ePoster Presentation Weighting: 30% Due date: Thursday August 18th 13.59pm each group Purpose: The purpose of this learning task is to choose one of the following global health issues that under the right conditions has or is likely to have a significant

Read More »

ISYS3375 Business Analytics

School of Business, IT and Logistics — ISYS3375 Business Analytics Assessment 2: Case Study Assessment Type: Individual report                                               Word limit: 2000-3000 (+/– 10%) Each Table or Figure is counted as Due date: Sunday of Week 5 23:59 (Melbourne time) Weighting: 35% 50 words + the number of words in its

Read More »

NURBN3032 Task 2: Managing a Transition to Practice Issue

NURBN3032 Task 2: Managing a Transition to Practice Issue Weight: 60% Due: Thursday 18th May (Week 11) In this task, students are required to demonstrate knowledge relating to understanding and addressing a transitional issue that can affect new graduate nurses. Using evidence from current scholarly literature (i.e., less than seven

Read More »

ATS2561 Sex and the Media

Assessment Guide – Research Essay Due: Friday Week 12, submit on Moodle Weighting: 40% Length: 2000 words Write an essay responding to one of the following questions/topics: ‘objectifying’ images might be different, or that they should be understood as the same, for men and women. Your argument should address why

Read More »

ITC597 Digital Forensics

ITC597 Digital Forensics – SAMPLE EXAM ONLY This paper is for Distance Education (Distance), Port Macquarie, Study Centre Sydney and Study Centre Melbourne students. EXAM CONDITIONS: NO REFERENCE MATERIALS PERMITTED No calculator is permitted No dictionary permitted WRITING TIME:                     2 hours plus 10 minutes reading time Writing is permitted during

Read More »

Simulation Project- Computer Lab Project

Model and analyse the communication tower at the Casuarina campus. Apply dead, live and wind load as per in AS 1170 or other relevant standards in SAP2000. You should measure size of the elements as far as you can from or make reasonable assumptions about the dimensions. Reasonable assumptions should

Read More »

COM621 UX Strategy

Solent University Coursework Assessment Submission Module Name:    UX Strategy Module Code:    COM621 Module Leader: Assessment Submission Date: Student Number: UX Strategy Contents Part 1 – Introduction to System (1K words) 2 1.0 Introduction. 2 1.1       Current SUAA UX Design and Business Model 2 1.2       Academic and Market Research. 3 1.3      

Read More »

MIT302 Internet of Things

Group Presentation and Video (part 2) Unit:             MIT302 Internet of Things Due Date:       09/06/2023 Total Marks:    This assessment is worth 10% of the full marks in the unit. Instructions: 1.        Students are required to cover all stated requirements. 3.        Please save the document as: MIT302_Firstname_Surname_StudentNumber[assessment1].ppt Requirements: Write a PowerPoint of

Read More »

Can't Find Your Assignment?

Open chat
Free Assistance
Universal Assignment
Hello 👋
How can we help you?