Clase 6: Detalles de la simulación

SANDER

EstructuraParámetros LEaP NMR, X-Ray,...QM, crystal data, experiments,... nucgen ( Construcción de ác. nucléicos ) resp ( Ajuste de cargas electrostáticas ) coordinate_filetopology_file Antechamber ( Set-up automatizado ) gibbssanderLES ( Estrategia especial de aumento de sampling conformaciona en MD ) ( Dinámica molecular)( Cálculo de diferencias de energía libre ) ptrajcarnalanalMM-PBSA Programas de análisis ( Procesado de trayectorias ) ( Análisis de energías )( Cálculo de energías libres ) Obtención de datos útiles en NMR intense spectrum fantasian profec ( Genera grids de reactividad basadas en energía libre ) nmode ( Análisis de modos normales )

EstructuraParámetros LEaP NMR, X-Ray,...QM, crystal data, experiments,... coordinate_filetopology_file SANDER ( Dinámica molecular) ptrajcarnalanalMM-PBSA Programas de análisis ( Procesado de trayectorias ) ( Análisis de energías )( Cálculo de energías libres )

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

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

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

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

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

Periodic Boundary Conditions (PBC)

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

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

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

Potential function Polarizable potentials IPOL. Inclusion of polarization IPOL. Inclusion of polarization –0 No polarization –1 Use polarization –2 Use polarization + 3 body interactions No recomendado para no expertos

Potential function Frozen/restrained atoms IBELLY: 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) NTR: Restraints in the Cartesian space (use harmonic restraints) –0 No restraints –1 MD with restraints on specific atoms

Energy minimization MAXCYC: Maximum number of cycles. MAXCYC: Maximum number of cycles. NCYC: After NCYC change from one method of optimization to other. NCYC: After NCYC change from one method of optimization to other. NTMIN: Method for minimization 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 DX0, DXM, DRMS: Details of minimization procedure: Use defaults

Molecular dynamics NSTLIM: Number of MD-steps per NRUN to be performed 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. NDFMIN: Number degrees of freedom to remove. If NTCM or NSCM.ne.0 use 6, otherwise 0. NTCM: 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) NSCM: Remove translational/rotational moves around center of mass every NSCN steps (def 0) T: Time at the start, default 0.0 T: Time at the start, default 0.0 DT: Integration time DT: Integration time

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

Regulación de la temperatura TEMP0: Reference temperature TEMP0: Reference temperature TEMPI: Starting temperature. Flag important when random velocities are generated. TEMPI: Starting temperature. Flag important when random velocities are generated. IG: Seed random number for velocity calculation IG: Seed random number for velocity calculation NTT: Temperature scaling NTT: Temperature scaling –0 Constant energy run. No scaling –1 Constant T. Use Berendsens 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 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 VLIMIT: IF.ne.0 when velocity of one atom is >VLIMIT set velocity=VLIMIT

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

SHAKE NTC: Flag to use SHAKE (In general a good idea for normal systems) 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 Å. TOL: Tolerance for coordinate resetting in SHAKE. Default Å.

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

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

PARTICLE MESH EWALD &ewald namelist &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

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, MARDIGRAS,... 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, MARDIGRAS,... Estas restricciones se introducen como flat harmonic restraints que se añaden al force- field. 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,... Es posible introducir otras restricciones más elaboradas: Time averaged restrains, noesy volumes, dipolar couplings,...

NMR REFINEMENT ISCALE: Number of additional variables to optimize (in addition to 3N coordinates) ISCALE: Number of additional variables to optimize (in addition to 3N coordinates) NOESKP: How often are the NOESY volumes computed NOESKP: How often are the NOESY volumes computed IPNLTY: 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 MXSUB: Number of submolecules to be use def 1

Restraints file IRESID (restraints definition) 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. 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 NSTEP1, NSTEP2 use restraints only between these two integration steps. Def uses always 0 IRSTYP: Absolute (0) or relative (1) restraints IRSTYP: Absolute (0) or relative (1) restraints

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

Restraints file La forma del restraints es un pozo plano (si IALTD=0, default) 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) Si R (valor en la simulación) –R 4. Liniar slope restraint –R2<R<R3 E=0 (flat) –Parabolic constraint otherwise La forma del restraints varia para IALTD=1 La forma del restraints varia para IALTD=1

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

Other restraints (used for NMR refinement) Es posible incluir restraints adicionales 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) Se puede activar opción LES (multiple- copies)