XPLOR

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X-PLOR
XPLOR minimizes the hybrid energy
function Ehybrid Echem wexpEexp where Echem
could be a molecular dynamics force
field (CHARMM, AMBER, OPLS/AMBER) a modified
geometric force field Engh/Huber, PROLSQ,
PARALLHDG and Eexp would be derived from Xray
data or NMR data
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Minimization Methods
Powells conjugate gradient minimization Molecular
dynamics numerical solution of Newtons equations
of motion with temperature variation simulated
annealing Rigid body dynamics Rigid body
minimization With respect to the coordinates or
some other properties (occupancies temperature
factors)
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Step 1 define topology(chemical (primary)
structure)
topology _at_TOPPARtopallhdg.pro end segment
name chain _at_TOPPARtophpep19.pro
sequence Ala Ala end end end write
structure outputdiala.psf end stop
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Calculate Energies
To minimize we need PSF file (Structure) energy
parameters starting coordinates XPLOR PDB format
structure _at_diala.psf end parameter
_at_TOPPARparallhdg.pro end coor _at_diala.pdb
end mini powell nstep50 end write coor
outputdialamin.pdb end stop
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Energy Function
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Molecular Dynamics
Molecular dynamics is the numerical solution of
Newtons equations of motion Fi mi ai mi
d2xi/dt2 d/dxi ETOTAL second order
differential equation masses mi are defined in
topology file ETOTAL is the XPLOR energy function
force field in parameter file and experimental
terms
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Verlet Dynamics
The Verlet algorithm is derived from a linear
approximation it is very simple and very
stable xi(th) xi(t) vi(t) h ½ ai
h2 xi(t-h) xi(t) - vi(t) h ½ ai h2 Add
(using Fiaimi) xi(th) 2xi(t) - xi(th)
Fi(t) h2/ mi velocities are calculated by vi(t)
½ h (xi(th) - xi(t-h))
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Langevin Dynamics
XPLOR can calculate Langevin dynamics mi
d2xi/dt2(t) -gradxi E fi(t) - mibi
dxi/dt(t) in addition to Newton equation
friction terms fi is a random force on atom
i mibi dxi/dt(t) is a velocity dependent
friction term with friction constant bi and is
used as temperature control
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T Control
Temperature control temperature
coupling Berendsens method for Langevin
dynamics with adjustable friction coeffcient and
zero random force bi bi0 ( T0/T -1) if T gtT0
bi is positive -gt cooling if TltT0 bi is negative
-gt heating Dynamics is initialized with random vi
s drawn from a Boltzmann distribution
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Slow Cooling
A slow cooling script evaluate (bath
1000) vector do (vx bath) (all) vector do (vy
bath) (all) vector do (vz bath)
(all) while (bath gt 50) loop cool evaluate
(bath bath - tempstep) dynamics verlet
nstep1000 time0.005
iasvelcurrent tcouptrue tbathbath
nprintnstep iprfrqntrfrq end end loop
cool
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Strategy
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Annealing Schedule
Evdw LJ or hard sphere repulsive potential
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E(NOE)
asymptote k(r-rupper) constant force
harmonic region (r-rupper)2
flat bottom rlower rupper
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More Energy Terms
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The Result a Bundle
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Assessing the Quality of NMR Structures
Number of experimental constraints RMSD of
structural ensemble (subjective!) Violation of
constraints Molecular energies Comparison to
structure database PROCHECK Compactness of
Structure, Hydrophobic Burial Back-calculation of
experimental parameters Ramachandran Quality