DINAMICA MOLECULARA
Transcript of DINAMICA MOLECULARA
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http://multimedia.mcb.harvard.edu/ ‘Inner life of a cell’
Studiul DINAMICII MOLECULARE: intelegerea comportamentului unei molecule la nivel atomic
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- Structura 3D
- Flexibilitatea (dinamica ) structurii 3D
+
- Interactiunea cu mediul- apa si/sau lipide
- Interactiunea cu liganzii
- Interactiunea cu alte proteine
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Amplitudine
Tipul miscarii Functionalitate Timp
MICA; <1 Å
Fluctuatii atomice; miscarea lanturilor
laterale
Acomodarea liganzilor
fs – ps
MEDIE; 1-5 Å
Miscarea buclelor
Modificarea situsului activ;
specificitatea de legare
ns
MARE; 5-10 Å
Miscarile domeniilor si a subunitatilor
Tranzitii alostericeµs – ms
GLOBALE; > 10 Å
Asocierea subunitatilor,
modificarea plierii
Functionalitatea proteinelor
ms – h
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Simulari de dinamica moleculara modelarea miscarilor de amplitudine mica si
medie permite adaugarea solventului si a membranei CHARMM, NAMD, AMBER
Analiza de moduri normale modelarea miscarilor colective (amplitudine
mare) permite studiul sistemelor cu un numar limitat
de atomi CHARMM
http://services.cbu.uib.no/tools/normalmodes
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TOPOLOGIA: tipurile de atomi, legaturile formate, sarcinile partiale ale resturilor, specificatiile de legare a resturilor + coordonate interne
PARAMETRII: valori numerice specifice pentru rezolvarea functiei empirice de energie – distante, unghiuri, improprii, diedre si constantele de forta la echilibru V=Vlegatura+Vnelegatura
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C:/Program Files/University of llinois/VMD/plugins/noarch/tcl/readcharmmpar1.1/par_all27_prot_lipid_na.inp
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Determinata experimental Cristalografie de raze X RMN
• lipsa atomilor de H
MINIMIZAREA ENERGIEI
Structurile cu energie mare – stari tranzitionale, instabile
• Modificarea coordonatelor atomilor in sensul descresterii energiei moleculei
•Variatia energiei in functie de coordonatele atomilor = profilul energetic al moleculei
• suprapunerea de atomi nelegati• legaturi si unghiuri deformate
- Adaugarea atomilor din coordonatele interne
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- distributia structurilor pe profilul energetic
-Conditia de minim energetic - ∆Energie~ 0
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simulari realiste – influenta ‘solventului’
Solvatare:VMD Main – Extensions – Modeling – Add Solvation Box
Utilizarea scripturilor de solvatare VMD Main – Extensions – Tk Console
Modelarea bistraturilor lipidice:VMD Main – Extensions – Modeling – Membrane Builder
apa lipide
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C:\MD\ubq
Psf – ul: informatii structurale (legarea atomilor)
‘topologia moleculei’ ubq.psf ( extensia Automatic PSF Builder)
Pdb – ul: coordonatele atomice ale sistemului ubq.pdb
VMD Main – Extensions – Tk ConsoleDirectorul de lucru (cd .. ; dir )source wat_sphere.tclsource wat_box.tcl
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In vid C:\MD\ubq: ubq.psf, ubq.pdb
VMD Main – Extensions – Simulation – NAMD Graphical
Interface
Edit – Other simulation parameters - Binary output files
Minimization
Run NAMD
VMD – Extensions – Analysis – NAMD Plot - *.out
*.coor - *_min.pdb
Cuantificarea modificarilor – RMSD (root mean square
deviation): VMD – Extensions – Analysis – RMSD Calculator
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Rezultatul: traiectoria de dinamica = set de conformatii *.dcd
C:\MD\ubq: ubq.psf, ubq.pdb
VMD Main – Extensions – Simulation – NAMD Graphical Interface
Edit – Other simulation parameters - Binary output files
Minimization Molecular dynamics
Run NAMD
Fluctuatiile moleculei:
-Dependenta de timp
-Amploarea
pozitie
viteza
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VMD Main – Extensions – Simulation – NAMD Graphical Interface – Edit
Ensemble – tipul de dinamica: NVE – Energie constanta
- temperatura (K)
Fixed atoms
Other simulation parametersDCD/XST output frequencyTime Step
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Incalzirea moleculei - treptatTemperatura – distributia vitezelorVitezele initiale ale atomilor – ‘arbitrare’
lipsa corelatiilor intre miscarea atomilor legati
Echilibrarea structurii – zeci-sute psCu rescalarea vitezelor in acord cu
temperatura
Fara a rescala vitezele
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Structura insuficient minimizataERORI
Simulare OK
Energia cinetica Temperatura
Rezultate de incredere:
- Sistemul de calcul echilibrat-Simulare stabila- Respectarea conditiei de energie constanta
Dinamica ‘utila’
VMD – Extensions –
Analysis – NAMD
Plot - *.out
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RMSD: VMD – Extensions – Analysis – RMSD Trajectory Tool
Distante:VMD - Mouse – Label – BondsVMD – Graphics – Labels – Bonds - Graph
UnghiuriVMD - Mouse – Label – AnglesVMD – Graphics – Labels – Angles - Graph
Punti de hidrogenVMD – Extensions – Analysis – Hydrogen bonds
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RMSD mediu / aminoacid
VMD Main – Extensions – Tk ConsoleDirectorul de lucru C:\MD\ubq (cd .. ; dir )source residue_rms.tcl (procedura de
calcu a RMSD mediu)set sel_resid [[atomselect top “protein and
apha] get resid]rmsd_residue_over_time top $sel_residresidue_rms.datColoring method - User
http://www.ks.uiuc.edu/Training/Tutorials/
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Conditii periodice
C:\MD\bsa\ bsa.psf BSA, apa + ioni
bsa.dcd: 20 ps Time step – 2 fs Distanta dintre frame-uri
0.2 ps Temperatura
1000 K – 300 K
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RMSD VMD – Extensions – Analysis – NAMD
Energy Interactiunea proteina (selection1) si apa
(selection2) Forta non-bonded
Alte analize ?