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M.Orozco J.L.Gelpí M.Rueda J.R.Blas

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  1. M.Orozco J.L.Gelpí M.Rueda J.R.Blas No a la Guerra

  2. Clase 6: Detalles de la simulación

  3. SANDER

  4. NMR, X-Ray,... QM, crystal data, experiments,... nucgen Estructura Parámetros ( Construcción de ác. nucléicos ) resp Antechamber ( Ajuste de cargas electrostáticas ) ( Set-up automatizado ) LEaP coordinate_file topology_file nmode Obtención de datos útiles en NMR ( Análisis de modos normales ) LES sander gibbs intense profec ( Estrategia especial de aumento de sampling conformaciona en MD ) ( Dinámica molecular) ( Cálculo de diferencias de energía libre ) spectrum ( Genera grids de reactividad basadas en energía libre ) fantasian Programas de análisis ptraj carnal anal MM-PBSA ( Análisis de energías ) ( Cálculo de energías libres ) ( Procesado de trayectorias )

  5. NMR, X-Ray,... QM, crystal data, experiments,... Estructura Parámetros LEaP coordinate_file topology_file SANDER ( Dinámica molecular) Programas de análisis ptraj carnal anal MM-PBSA ( Análisis de energías ) ( Cálculo de energías libres ) ( Procesado de trayectorias )

  6. Descripción general simulación • TIMLIM: Tiempo límite CPU simulación • IMIN: Decisión tipo cálculo • 0: Dinámica • 1: Minimización • NMROPT: Flag NMR • 0: No NMR restrains • >0: NMR restrains/weight changes • 2: NOESY volume restraints or chemical shifts restrains

  7. Nature & Format of the input • NTX: Read coordinates, velocities and box • 1: X formatted no V • 5: X and V are read formatted • 7: X,V and Box are read formatted • IREST: Flag to restart the run: • 0 No • 1 Restart (need X, V) • NTRX: Format for restraint from file refc • 0 unformatted • 1 formatted

  8. Nature & Format of the output • NTX0: Format for coordinates velocities and box • 1: X formatted • 0: unformatted • NTPR: Every NTPR mdifo will be printed. • NTWR: Every NTWR restart file will be written. • IWRAP: 1 Center solute in the primary box.

  9. Nature & Format of the output • NTWX, NTWV, NTWE: frequency of the output of coordinates, velocities, energies (If .ne. 0) • NTWXM, NTWVM, NTWEM: If .ne. 0 limits the output of coordinates, velocities, energies • NTWPRT: archive limit flag (V,X) • 0 all atoms • <0 only solute • >0 only atoms 1NTWPRT

  10. Potential function • NTF Force evaluation • 1: complete interaction • 2: bonds involving H are omitted • 3: all the bonds are omitted • ... • NTB Periodic boundary conditions • 0: No periodicity • 1: Constant volume • 2: Constant pressure

  11. Periodic Boundary Conditions(PBC)

  12. Potential function • DIELC: multiplicative factor for dielectric constant default 1.0. See options in GB/SA • CUT: Cutoff for non-bonded interactions. See Ewald • SCNB: Scaling of 1-4 vW interactions (1/SCNB). Default 2 • SCEE: Scaling of 1-4 electrostatic (1/SCEE). Default 1.2

  13. Potential functionGB calculations • IGB: Use of generalized Born model (GB) IGB=0 no GB, IGB=1., IGB=2 (vacuum calculation), IGB=3 (vacuum distance dependent dielc const.) • GBPARM: 1 (Beveridge), 2 (Case) Two sets of GB parameters • READRAD: if .ne.0 read vW radii for GB calculations • OFFSET: fine tune of Born radii defaults 0.09 or 0 • IGBFREQ: Frequency of update of Born radii • GBSA: If .eq.1 SA corrections to GB. • SURFTEN: Use non-default surface tension.

  14. Generalized Born Método de introducir solvente continuo Técnica potente pero poco contrastada No recomendada para no expertos

  15. Potential functionPolarizable potentials • IPOL. Inclusion of polarization • 0 No polarization • 1 Use polarization • 2 Use polarization + 3 body interactions No recomendado para no expertos

  16. Potential functionFrozen/restrained atoms • IBELLY: • 0 normal run • 1 Belly run. Only a set of atoms (specified later) are allowed to move • NTR: Restraints in the Cartesian space (use harmonic restraints) • 0 No restraints • 1 MD with restraints on specific atoms

  17. Energy minimization • MAXCYC: Maximum number of cycles. • NCYC: After NCYC change from one method of optimization to other. • NTMIN: Method for minimization • 0 Conjugate gradient • 1 For NCYC steepest descent then CG • 2 Only steepest descent • DX0, DXM, DRMS: Details of minimization procedure: Use defaults

  18. Molecular dynamics • NSTLIM: Number of MD-steps per NRUN to be performed • NDFMIN: Number degrees of freedom to remove. If NTCM or NSCM.ne.0 use 6, otherwise 0. • NTCM: • 0 Do not remove translational/rotational moves around center of mass • 1 Remove at the beginning • NSCM: Remove translational/rotational moves around center of mass every NSCN steps (def 0) • T: Time at the start, default 0.0 • DT: Integration time

  19. Etapa de integración • Si no constraints en ningún enlace 0.0005 ps. • Si constraints (SHAKE) en enlaces X-H 0.001 ps • Si constraints en todos los enlaces 0.002 • Si el sistema esta muy tensionado, T o P es elevada usar 0.001 ps • Reducir la etapa de integración aumenta linealmente el costo de la simulación pero puede ser necesario para evitar discontinuidades

  20. Regulación de la temperatura • TEMP0: Reference temperature • TEMPI: Starting temperature. Flag important when random velocities are generated. • IG: Seed random number for velocity calculation • NTT: Temperature scaling • 0 Constant energy run. No scaling • 1 Constant T. Use Berendsen’s coupling • 4 When T deviates from TEMP0 more than DTEMP scale velocities, otherwise do not scale • TAUTP: Time constant for heat bath coupling: Default 1.0. Smaller value tighter coupling • VLIMIT: IF .ne.0 when velocity of one atom is >VLIMIT set velocity=VLIMIT

  21. Regulación de la presión(NTB=2) • NTP: Flag for constant pressure dynamics • 0 no constant pressure • 1 MD isotropic scaling • 2 MD anisotropic scaling • PRES0: Pressure (1 atm default). • COMP: Compressibility of the system. In general use water value (44.6) • TAUP: Pressure relaxation time (0.2 ps) • NPSCAL: Modelo de escalado posiciones • 0: atom scaling: can compress bonds. • 1: Molecule scaling

  22. SHAKE • NTC: Flag to use SHAKE (In general a good idea for normal systems) • 1 Do not use SHAKE • 2 SHAKE on X-H bonds • 3 SHAKE on all the bonds • TOL: Tolerance for coordinate resetting in SHAKE. Default 0.0005 Å.

  23. WATER CAP(gota de agua) • IVCAP: • 0 in effect if defined in parm • 1 Cap in effect, but pointer will be modified (MATCAP) • 2 Cap will be inactivated • FCAP: • Force constant for Cap (half harmonic). Default 1.5 kcal/mol Å2

  24. PARTICLE MESH EWALD • Es una técnica muy poderosa para incluir interacciones electrostática de largo alcance. • Es totalmente necesaria para simular DNA • Recomendable para proteínas, sobre todo si están muy cargadas • Sobreestima la periodicidad de la simulación. • Últimas versiones de AMBER lo toman como defecto de la simulación.

  25. PARTICLE MESH EWALD • &ewald namelist • A,B,C. The PME unit cell • Alpha,Beta,GAMMA: Cell angles • NFFT1,NFFT2,NFFT3: Size of charge grid. In general choose =A,B,C i.e grid spacing 1 Å • Use defaults for all the other parameters

  26. NMR REFINEMENT • La mayoría de usuarios usa MD solo para refinar la geometría a partir de las restricciones de distancias o ángulos derivadas a partir de otros programas DIANA,... • Estas restricciones se introducen como “flat harmonic restraints” que se añaden al force-field. • Es posible introducir otras restricciones más elaboradas: Time averaged restrains, noesy volumes, dipolar couplings,...

  27. NMR REFINEMENT • ISCALE: Number of additional variables to optimize (in addition to 3N coordinates) • NOESKP: How often are the NOESY volumes computed • IPNLTY: • 1 minimize the abs value of errors (R-factor) • 2 minimize the RMS (sum square errors) • 3 Special treatment for NOESY intensities • MXSUB: Number of submolecules to be use def 1

  28. Restraints file • IRESID (restraints definition) • 0 global atom numbers • 1 global residue number • IAT(1)IAT(4) if IRESID=0 atoms to restraints (IAT(3)=0, distance, IAT(4)=0 angle, otherwise torsion). If IRESID=1 residue number, then ATNAM(1)ATNAM(2) define the atom #s. • NSTEP1, NSTEP2 use restraints only between these two integration steps. Def uses always 0 • IRSTYP: Absolute (0) or relative (1) restraints

  29. Restraints file • IALTD: Ignore large violation if 1. If 0 (default) not ignore • IFVARI: Change force or target value along the trajectory (R1AR4A, RK2ARK3A. • NINC, IMULT: Define how the target/force values change along the trajectory (use defaults).

  30. Restraints file • La forma del restraints es un pozo plano (si IALTD=0, default) • R1R4; RK2RK3; R1AR4A; RK2RK3 • Si R (valor en la simulación) • R<r1 o R>4. Liniar slope restraint • R2<R<R3 E=0 (flat) • Parabolic constraint otherwise • La forma del restraints varia para IALTD=1

  31. Restraints file • IGR1(i),i=1200. IGR2(i), =1200. Se usan para definir restraints sobre un grupo de átomos. Se calculan promedio de posiciones con esas listas

  32. Other restraints (used for NMR refinement) • Es posible incluir restraints adicionales • NOESY volume restraints • Chemical shifts restraints • Direct dipolar coupling restraints • Restraints de quiralidad • Time-averaged constraints • Se puede activar opción LES (multiple-copies)