Structure modification

Mutate Residue

WS: mutateResidueFromPDBText

Mutate a Residue from a structure given in PDB format

Program: VMD.

Set-up for Simulation

Check for disulphide bonds

WS: addDisulphideBondsFromPDBText

• Distance Cutoff: 2.5 Å
• SS bonds added to the PDB data as a REMARK.

Clean PDB

WS: cleanStructureFromPDBText

• Remove Crystal Waters.
• Remove Crystal Hydrogens.
• Remove Non-Parametrized Ligands.

Fix Side Chains

WS: fixSideChainsFromPDBText

Fix Side Chain Problems, adding missing heavy atoms (if possible).

Program: Leap (Ambertools).

Add structural water molecules and ions

WS: titrateStructureFromPDBText

Add structural water molecules and ions in the energetically most favourable positions at the surface of the structure.

Program: CMIP, Classical Molecular Interaction Potentials.

• By default, necessary ions (Positive ions: Na+. Negative Ions: Cl- ) are added in order to neutralize the system.

Set ionization state

Set the appropriate ionization states according to pH

Programs: ProtPka (Fast). CMIP (Slow)

Only Histidine residues

WS: protonateHistidinesFromPDBText

All ionizable residues

Energy Minimization (Hydrogen Atoms)

Energy minimization of hydrogen atoms keeping all heavy atoms fixed to their original positions

NAMD

WS: optimizeStructureFromNAMD_MD_Structure

Usable for both AMBER and CHARMM topologies

• Available types of minimization: Conjugate Gradients.

GROMACS

WS: optimizeStructureFromGROMACS_MD_Structure

• Available types of minimization: Conjugate Gradient and Steepest Descent.

Energy Minimization (All atoms)

Possibility of restraining atom movements with a given force constant.

NAMD

WS: optimizeStructureFromNAMD_MD_Structure

Usable for both AMBER and CHARMM topologies

Programs: namd2 from NAMD Package.

• Type of minimization: Conjugate Gradients.

GROMACS

WS: optimizeStructureFromGROMACS_MD_Structure

Programs: grompp and mdrun from Gromacs Package.

• Types of minimization: Conjugate Gradient and Steepest Descent.

Solvate Structure

Adds a solvent shell to the system according to the specific settings. By default, the necessary ions (Positive ions: Na+, Negative Ions: Cl-) are added in order to neutralize the system

AMBER

WS: solvateStructureFromAMBER_MD_Structure

Structure Solvation in Amber.

Program: Leap (Ambertools)

• Available box types:: Shell, Spheric, Cubic and Truncated Octahedron.
• Box size specified by Å of spacing distance around the molecule.
• Water molecule type: TIP3P

NAMD

WS: solvateStructureFromNAMD_MD_Structure

• Available box types: Cubic, and Spheric.
• Box size specified by Å of spacing distance around the molecule.
• Water molecule type: TIP3P.

GROMACS

WS: solvateStructureFromGROMACS_MD_Structure

• Available box types: Cubic, Triclinic, Dodecahedron and Truncated Octahedron.
• Box size specified by nanometers of spacing distance around the molecule.
• Water molecule type: SPC.

Molecular Dynamics simulations

Simple Box Solvent System Equilibration (NPT, NVT, or NVE)

Simple Box Solvent Molecular Dynamics (NPT, NVT, or NVE)

• Particle Mesh Ewald (PME) for full-system periodic electrostatics.
• Available Ensembles: NPT, NVT, NVE

NAMD - Amber

WS: runMDFromAMBER_MD_Structure

Program: namd2 from NAMD package.
ForceField: Amber Parm99SB* for Proteins, Amber Parm99bsc0 for Nucleic Acids (DNA/RNA)

• Constant temperature dynamics via Langevin Dynamics.
• Constant pressure dynamics via Nose-Hoover Langevin piston.
• SHAKE is used to maintain all bonds involving hydrogen atoms at their equilibrium value

NAMD - Charm

WS: runMDFromNAMD_MD_Structure

Program: namd2 from NAMD package.
Forcefield: Charmm

• Constant temperature dynamics via Langevin Dynamics.
• Constant pressure dynamics via Nose-Hoover Langevin piston.
• SHAKE is used to maintain all bonds involving hydrogen atoms at their equilibrium values

GROMACS

WS: runMDFromGROMACS_MD_Structure

Program: mdrun from Gromacs package.

• Constant temperature dynamics via Velocity-rescale algorithm.
• Constant pressure dynamics via Parrinello-Rahman algorithm.
• LINCS Linear Constraint Solver was used to maintain all bonds at their equilibrium values.

Coarse Grained Molecular Dynamics Simulations

Coarse-Grained MD: Brownian Dynamics (C-Alpha)

WS: runBrownianMDFromPDBText

Protein is put in a stochastic bath that keeps the temperature constant and modulates the otherwise extreme oscillations of the residues. This bath is simulated with two terms accounting for a velocity-dependent friction and stochastic forces due to the solvent environment. The potential energy used to compute forces assumes a coarse-grained representation of the protein (Calpha-only) and a quasi-harmonic representation of the interactions.

• Time: total simulation time.
• Delta_t: Time ellapsed between two consecutive time steps.
• Output Frequency: Number of frames after which a frame is written and considered for analysis.
• Force Constant: Measure of the strength of the spring connecting atoms measured in Kcal/mol*Ų.

Coarse-grained MD: DISCRETE dynamics (C-Alpha)

WS: runDiscreteMDFromPDBText

Protein is modelled as a system of beads (Calpha atoms) interacting through a discontinuous potential (square wells). Outside the discontinuities, potentials are considered constant, thereby implying a ballistic regime for the particles (constant potential, constant velocity) in all conditions, except at such time as when the particles reach a potential discontinuity (event or collision). At this time, the velocities of the colliding particles are modified by imposing conservation of the linear momentum, angular momentum, and total energy. DMD has a major advantage over techniques like MD because, as it does not require the integration of the equations of motion at fixed time steps, the calculation progresses from event to event.

• Time: total simulation time.
• Delta_t: Time ellapsed between two consecutive time steps.
• Cut-off Distance: Maximum distance for the pairs of atoms to be included in the calculation.
• Sigma is the well amplitude for consecutive Calpha atoms.
• Sigma Go is the well amplitude for non-consecutive Calpha.

Coarse-grained MD: DISCRETE dynamics (Heavy atoms)

WS: runDiscreteMD_AA_FromPDBText

Protein is modelled as a system of beads (ALL Heavy Atoms) interacting through a discontinuous potential (square wells). Outside the discontinuities, potentials are considered constant, thereby implying a ballistic regime for the particles (constant potential, constant velocity) in all conditions, except at such time as when the particles reach a potential discontinuity (event or collision). At this time, the velocities of the colliding particles are modified by imposing conservation of the linear momentum, angular momentum, and total energy. DMD has a major advantage over techniques like MD because, as it does not require the integration of the equations of motion at fixed time steps, the calculation progresses from event to event.

• Time: total simulation time.

Coarse-grained MD: NMA (C-Alpha)

WS: runNormalModeAnalysisFromPDBText

Normal Mode Analysis (NMA) can be defined as the multidimensional treatment of coupled oscillators from the analysis of force-derivatives in equilibrium conformations. This methodology assumes that the displacement of an atom from its equilibrium position is small and that the potential energy in the vicinity of the equilibrium position can be approximated as a sum of terms that are quadratic in the atomic displacements. Vectorial Anisotropic Network Model using coarse-grained (Calpha) protein representation is the formalism implemented here. Through the diagonalization of the hessian matrix, the ANM provides eigenvalues and eigenvectors that not only describe the frequencies and shapes of the normal modes, but also their directions.

Possibility to choose between three ANM formalism definitions of the force constants:

• 1. Linear algorithm uses a unique potential is used for all interactions considered.
• 2. Kovacs algorithm uses a distance-dependent potential.
• 3. Mixed algorithm uses a potentials adjusted to atomistic MD simulations.

• Force Constant: Measure of the strength of the spring connecting atoms measured in Kcal/mol*Ų.
• Cutoff: Maximum distance for the pairs of atoms to be included in the calculation.

Molecular Dynamics Trajectory Standard Cartesian Analysis

Plot RMSd along the trajectory

WS: getTrajectoryRmsFromMD_Trajectory

Root Mean Square deviation along the trajectory.

Programs: Ptraj from AmberTools package (Binpos,Crd,DCD,NetCDF trajectory formats). g_rms from Gromacs package (XTC trajectory format).

• Possibility to select a subset of atoms/residues from the whole system.
• User defined Mask only available for ptraj-compatible trajectory formats (Binpos,Crd,DCD,NetCDF).

Plot RMSd x Residue

WS: getTrajectoryRmsPerResidueFromMD_Trajectory

Average Root Mean Square deviation per residue along the trajectory.

Programs: Ptraj from AmberTools package (Binpos,Crd,DCD,NetCDF trajectory formats). g_rmsf from Gromacs package (XTC trajectory format).

• Possibility of use a reference structure (PDB format).
• Possibility to select a subset of atoms/residues from the whole system.
• User defined Mask only available for ptraj-compatible trajectory formats (Binpos,Crd,DCD,NetCDF).

Plot BFactor per residue

WS: getTrajectoryBfactorPerResidueFromMD_Trajectory

Gets Bfactor values per residue from a Trajectory.

Programs: Ptraj from AmberTools package (Binpos,Crd,DCD,NetCDF trajectory formats). g_rmsf from Gromacs package (XTC trajectory format).

• Possibility to select a subset of atoms/residues from the whole system.
• User defined Mask only available for ptraj-compatible trajectory formats (Binpos,Crd,DCD,NetCDF).

Plot Radius of Gyration along the trajectory

WS: getTrajectoryRadiusOfGyrationFromMD_Trajectory

• Possibility to select a subset of atoms/residues from the whole system.
• User defined Mask only available for ptraj-compatible trajectory formats (Binpos,Crd,DCD,NetCDF).

Trajectory format conversions

Compress trajectory to PCZ

WS: zipTrajectory

• Quality param: Specifies the quality of the compression as a percentage of explained variance (default 90%)
• Gaussian RMSd param: weighted RMSd, giving less weight to atoms in flexible regions (e.g. loops).
• Number of Eigen Vectors Param: Specifies the number of eigenvectors that must be stored in the file. With 0 value pcazip will get the necessary number of vectors to obtain the percentage of explained variance (quality param).

Decompress PCZ trajectory

WS: unzipTrajectory

Uncompress trajectory from PCZ format to CRD format.

Program: pcazip (https://mmb.pcb.ub.es/software/pcasuite).

Convert trajectory to a set of PDB Files

WS: fromMD_TrajectoryToPDB_Collection

Program: ptraj from Ambertools package.

Convert trajectory to BINPOS Format

WS: fromMD_TrajectoryToMD_TrajectoryBINPOS

Program: ptraj from Ambertools package. BINPOS is the Scripps Binary format.

Converts trajectory to CRD Format

WS: fromMD_TrajectoryToMD_TrajectoryCRD

Program: ptraj from Ambertools package. CRD: Amber ASCII format.

Converts trajectory to DCD Format

WS: fromMD_TrajectoryToMD_TrajectoryDCD

Converts trajectory to NetCDF Format

WS: fromMD_TrajectoryToMD_TrajectoryNetCDF

Flexibility Analysis

Flexibility Analysis

WebServer: FlexServ

• Principal Components.
• Variance Profile.
• B-factors Landscape.
• Lindemann Coefficients.
• Apparent Stiffness.
• Hinge Point Prediction.
• Residue Correlations.
• Collectivity Indexes.

Trajectory manipulation

Programs: Ptraj from AmberTools package (Binpos,Crd,DCD,NetCDF trajectory formats). g_rmsf from Gromacs package (XTC trajectory format).

• Possibility to select a subset of atoms/residues from the whole system.
• User defined Mask only available for ptraj-compatible trajectory formats (Binpos,Crd,DCD,NetCDF)

Get Average Structure

WS: getAverageStructureFromMD_Trajectory

Get a trajectory fragment

WS: getSliceFromMD_Trajectory

Gets a set of snapshots from a Trajectory.

Get a trajectory snapshot

WS: getSnapshotFromMD_Trajectory

Remove Water molecules and ions from trajectory

WS: getDryTrajectoryFromMD_Trajectory

Return trajectory for a set of atoms

WS: getMaskTrajectoryFromMD_Trajectory