Electrostatic Potential (ESP) Measure polarization Electron Map density Electron distribution Dipole Moment Measure bond length/angle Measure bond strength Organic software for 3D model Click here download Rasmol Click here download PyMol Click here download Jmol Click here Chem EDDL Click here chemical search. Click here CRC database Modelling and 3D representation Chemistry Database Click here Spectra database(OhioState) Click here Spectra database (NIST) Click here chem finder. Spectroscopic Database Click here down Swiss PDB Modelling and 3D representation Click here crystallography database ✓ ✓ Click here NIST data ✓ Click here download Arguslab Click here chem axon Click here download Avagrado Click here chem EdDL Click here download chimera ✓
12
Embed
IB Chemistry on ICT, 3D software, Chimera, Jmol, Swiss PDB, Pymol for Internal Assessment on Hemoglobin and Myoglobin
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Electrostatic Potential (ESP)Measure polarizationElectron Map densityElectron distribution
Dipole MomentMeasure bond length/angle
Measure bond strength
Organic software for 3D model
Click here download Rasmol
Click here download PyMolClick here download Jmol
Click here Chem EDDL
Click here chemical search. Click here CRC database
Modelling and 3D representation
Chemistry Database
Click here Spectra database(OhioState) Click here Spectra database (NIST)
Type PDB code – 4HHBRight click – select Hetero Select - HETATM – HEM
4 Heme is display from 4 chains
Measure bond length/angleMeasure number H2 bonds
Measure bond strengthProtein 1, 2 , 3O structure
Presence of disulfide bondPresence alpha and beta pleated sheet
Click here J mol protein video
Chemical viewer 3D structure (Jmol)
Uses molecular modelling
1
J mol executable file
Measure distance
Select measure – distance for porphyrin ringMeasure ring size/distance Fe from planeSelect protein – by residue – HistidineMeasure and locate His F8 Measure and locate His E7
-What is the distance bet Fe and His E7 and F8, and are they the same for diff heme found in hemoglobin/myoglobin-Is His E7/F8 orientation similar for Oxy, Deoxy and Myoglobin.-Is there any differences bet distance/position/orientation of porphyrin ring for Hemoglobin and Myoglobin-How is Fe2+ located, along or out of plane for Hemo/Myoglobin-Is the distance bet Fe and ligand N of porphyrin the same for Hemoglobin/Myoglobin-Is structure/size of porphyrin ring same for α and β chain-Is there any variation in terms of Fe and His E7/F8 for fetal hemoglobin and sickle cell hemoglobin-Why His E7 and F8 are located in such a way across many different species? Are their orientation highly conserved and why?
Click here NCBIClick here UCSC
Click here Ensembl
Structural similarity and differences bet Hemoglobin and Myoglobin
Myoglobin hemoglobin
Vs
Hemoglobin Chimera Pymol Jmol Swiss PDB Mean
Orientation His/Fe Similar Similar Similar Similar Similar
Bond length N - Fe 2.12A 1.90A 2.02A 2.02A 2.01A
Bond length Fe – E7 5.93A 5.80A 5.45A 5.42A 5.55A
Bond length Fe – F8 2.25A 2.05A 2.10A 2.21A 2.13A
Chimera Swiss PDB
Data source
Myoglobin Chimera Pymol Jmol Swiss PDB Mean
Orientation His/Fe Similar Similar Similar Similar Similar
Possible Research Question Data Collection using 3D modelling
Data Collection using Database
Click here Jmol Click here PyMol
Click here NCBIClick here UCSC
Click here Ensembl
Structural similarity and differences bet Hemoglobin and Myoglobin
Myoglobin hemoglobin
vs
Chimera Swiss PDB
Evaluation and Limitation using 3D modelling
Must use a variety of sources/programme to verify/validate the validity and reliability of data collectedAverage is computed from diff software and checked with database to confirm.Check on methodological limitation using 3D model. (MUST perform 3D Optimization to most stable form structure.Critical and skeptical of result produced by computational chemistry. Major limitation of computation, they assume non-interacting molecule. (Ideal situation, ex molecule in vacuum or isolated state)Most appropriate molecule are those whose coordinates are not theoretical but derive from experimental structural determination(using X ray diffraction)Be careful of predicted arrangement from simulation /3D modelData sources are supported using diff method/3D model/databaseCertain database like NIST and CRC are more reliable source Check if there is a good agreement bet CRC, diff databases and 3D model prediction before making conclusionComputation programme is always based on approximation and we cannot conclusive prove anythingReflect of validity and reliability of dataIs model a true representation of reality?
-What is the distance bet Fe and His E7 and F8, and are they the same for diff heme found in hemoglobin/myoglobin-Is His E7/F8 orientation similar for Oxy, Deoxy and Myoglobin.-Is there any differences bet distance/position/orientation of porphyrin ring for Hemoglobin and Myoglobin-How is Fe2+ located, along or out of plane for Hemo/Myoglobin-Is the distance bet Fe and ligand N of porphyrin the same for Hemoglobin/Myoglobin-Is structure/size of porphyrin ring same for α and β chain-Is there any variation in terms of Fe and His E7/F8 for fetal hemoglobin and sickle cell hemoglobin-Why His E7 and F8 are located in such a way across many different species? Are their orientation highly conserved and why ?
- Porphyrin gp of heterocyclic made of 4 pyrrole subunit- Porphyrin macrocycle has 26 (delocalized) pi electron, obey Hückel rule - It is aromatic, 4n+2 π. (Highly conjugated system)
Heme
PorphyrinHeme = Fe + porphyrins ring
Heme
Heme A Heme B Heme C
Mitochondria- cytochrome c oxidase- electron transport
Hemoglobin A - 2 alpha and 2 beta chainsHemoglobin A2 - 2 alpha and 2 delta chainsHemoglobin F - 2 alpha and 2 gamma chainsHeme (porphyrin) bind to Fe2+ using 4 nitrogen atom (histidine gp) Porphyrin
- as electron-pair donor - polydentate ligandFe form 2 additional bonds, one on each side of the heme plane. These binding sites call fifth and sixth coordination sites. This hisitidine is referred as proximal Histidine F8The sixth coordination site bind oxygen with His E7 nearby
Deoxygenated hemoglobin formFe2+ - out planeCan’t fit the ring
Fe bind to six ligand. 4 with N atom of porphyrinFifth ligand is donated by His 93 (F8) O2 add to Fe as sixth ligandO2 tilt relative to perpendicular of heme plane
Fe bind to six ligand. 4 with N atom of porphyrinFifth ligand is donated by His F8 O2 add to Fe as sixth ligandO2 tilt relative to perpendicular of heme plane
His E7 locate over Fe, force CO to bind to Fe at an angle. This steric hinderance reduce afinity of CO in hemoglobin. O2 bind to Fe at an angle, its binding not affected by presence of His E7.