diff --git a/docs/images/TutorialSMD2_1.png b/docs/images/TutorialSMD2_1.png new file mode 100644 index 0000000..ccfabb5 Binary files /dev/null and b/docs/images/TutorialSMD2_1.png differ diff --git a/docs/source/Background SIRAH.rst b/docs/source/Background SIRAH.rst index 9546485..ec45eec 100644 --- a/docs/source/Background SIRAH.rst +++ b/docs/source/Background SIRAH.rst @@ -97,11 +97,11 @@ Available multiscale implementations in SIRAH: - An all-atoms/CG model covalently linking both resolutions within a nucleic acid chain (see [:ref:`13 `]); -- A multiresolution solvent model allowing the mixture of fully atomistic solutes with a shell of atomistic solvent surrounded by CG water, applicable to highly solvated systems like viral capsids (see [:ref:`14 `]). +- A multiresolution solvent model allowing the mixture of fully atomistic solutes with a shell of atomistic solvent surrounded by CG water, applicable to highly solvated systems like viral capsids (see [:ref:`7 `]). -- A triple solvation scheme, treating water at all-atoms, CG, and supraCG levels, is also available (see [:ref:`14 `]). +- A triple solvation scheme, treating water at all-atoms, CG, and supraCG levels, is also available (see [:ref:`7 `]). -This is particularly useful for complex cellular systems and has been applied to assemble and simulate VLPs systems in an onion-shaped configuration using CG water (WT4) and supra-CG solvent (WLS) (**Figure 6**) (see [:ref:`10 `] and [:ref:`14 `]). +This is particularly useful for complex cellular systems and has been applied to assemble and simulate VLPs systems in an onion-shaped configuration using CG water (WT4) and supra-CG solvent (WLS) (**Figure 6**) (see [:ref:`7 `] and [:ref:`10 `]). @@ -268,15 +268,5 @@ References :alt: Citation :target: https://scholar.google.com/scholar?cites=5473055142318037579 -.. _ref14: -[14] Machado, M. R.; González, H. C.; Pantano, S. MD Simulations of Virus like Particles with Supra CG Solvation Affordable to Desktop Computers. Journal of Chemical Theory and Computation 2017, 13, 5106–5116. |MC1| |MC1-cit| - -.. |MC1| image:: https://img.shields.io/badge/DOI-10.1021%2Facs.jctc.7b00659-blue - :alt: Access the paper - :target: https://doi.org/10.1021/acs.jctc.7b00659 - -.. |MC1-cit| image:: https://img.shields.io/endpoint?url=https%3A%2F%2Fapi.juleskreuer.eu%2Fcitation-badge.php%3Fshield%26doi%3D10.1021%2Facs.jctc.7b00659 - :alt: Citation - :target: https://scholar.google.com/scholar?cites=16637391138490147245 diff --git a/docs/source/Background SIRAH_complete.rst b/docs/source/Background SIRAH_complete.rst deleted file mode 100644 index 255f38f..0000000 --- a/docs/source/Background SIRAH_complete.rst +++ /dev/null @@ -1,266 +0,0 @@ -Background -================== - -In recent decades, the field of molecular dynamics (MD) simulations has undergone significant progress and development, allowing for the investigation of biological systems at nanoseconds to microsecond scales. However, complex systems involving millions of atoms or large-size protein assemblies are still too computationally expensive to be studied in atomistic detail without the aid of specialized supercomputers. Thus, the computational cost associated with MD simulations has driven the development of cost-effective approximations, particularly Coarse-Grained (CG) models, which attempt to increase system complexity and spatiotemporal sampling. The resolution of CG models has become essential for investigating molecular processes at the nano and meso dimensions and addressing mechanisms that have been previously inaccessible to traditional modeling methods. CG models consist of effective particles, referred to as beads, that represent groups of corresponding atoms. CG models can vary in resolution, ranging from supra-CG levels where a single bead represents an entire protein, to near-atomistic models that preserve most of the chemical characteristics [:ref:`1 `]. - -Currently, one of the most prominent CG models is the `SIRAH `_ (Southamerican Initiative for a Rapid and Accurate Hamiltonian) force field, which was developed by the `Biomolecular Simulations Group `_ `Institut Pasteur de Montevideo `_. It covers parameters and topologies for aqueous solvent, phospholipids, DNA, metal ions, and proteins. A recent update introduced modifications to bonded and non-bonded parameters, protonation states, post-translational modifications, and compatibility improvements for different force fields [:ref:`2 `]. - - -The SIRAH force field for CG simulations ------------------------------------------ - -The distinguishing features of the SIRAH force field for CG simulations lie in its approach to mapping from atomistic to CG representations and its strategic selection of interaction potentials. The mapping procedure entails strategically placing effective interactive beads at pivotal atoms involved in the structure or at atoms that form crucial intermolecular interactions (**Figure 1**). The distribution of these beads corresponds to intended interactions of functional groups based on size and charge, resulting in a heterogeneous distribution with higher bead density in regions that establish more diverse interactions. - -.. figure:: ../images/mousepad-old.png - :align: center - :width: 100% - - **Figure 1.** SIRAH force field CG representation. - -SIRAH employs a classical two-body Hamiltonian, facilitating its use in various MD engines without the need for extensive learning or format changes. This choice enables anyone familiar with standard all-atoms MD simulations in engines like AMBER or GROMACS to run CG simulations using SIRAH seamlessly. The classical Hamiltonian requires the determination of numerous parameters, but SIRAH's mapping strategy significantly reduces this burden. Equilibrium distances are derived directly from statistical data, quantum-level calculations, or canonical conformations, minimizing the number of parameters to be determined. - -The initial CG model for DNA served as the foundation for SIRAH, with force constants, partial charges, and Lennard-Jones (LJ) parameters derived through trial and error simulations on DNA segments. The approach of transferring and adapting parameters based on similar functional groups ensures analogous interaction parameters for diverse molecular moieties. SIRAH's versatility is exemplified through its CG models for different biomolecular families. In the following sections, we provide a synopsis of the CG models developed by SIRAH; however, for a more comprehensive material, please refer to [:ref:`3 `]. - - -The CG DNA model ------------------ - -The SIRAH's DNA model involves six effective beads representing each of the four CG nucleotides (**Figure 2**) [:ref:`4 `]. The mapping strategy considers the 5' - 3' prime polarity and electrostatic complementarity between A-T and G-C base pairs. The backbone is represented by two beads at the phosphate and C5' Carbon positions, while three beads on the Watson-Crick edge ensure base pair recognition. The five-membered sugar ring is depicted by a single bead situated at the C1' position, linking the backbone to the Watson-Crick edge. - -.. figure:: ../images/mousepad-old-dna.png - :align: center - :width: 80% - - **Figure 2.** SIRAH force field DNA CG representation. - -By selecting this mapping option, the specific base-pair recognition of the B-form DNA is maintained, and the distortion effects of mismatches are captured precisely. However, it has limitations, since it excludes less frequent inter-nucleotide interactions, such as sugar edge or Hoogsteen base pairs. - -In SIRAH's DNA model, bead sizes determined by LJ parameters are heterogeneous, maintaining correct stacking distances in a double-stranded configuration. The effective beads representing bases adopt LJ sizes from the Barcelona force field, while those representing the backbone have larger sizes. The partial charges, assigned to ensure electrostatic recognition, are determined to reproduce the electrostatic potential of the force field in the grooves of a double-stranded structure. The initial mass distribution allows MD simulations with a timestep of 5 fs. - -This CG DNA model reproduces the structure and dynamics of double-stranded DNA comparable to atomistic force fields and demonstrates spontaneous formation of large "bubbles" within DNA, fraying, rehybridization, and matches experimentally determined persistence lengths of single-stranded filaments [:ref:`4 `]. - - -The WatFour model for CG explicit solvent ------------------------------------------------- - -In tandem with the DNA model development, a CG aqueous solvent was created, featuring CG water and monovalent electrolytic ions (sodium, potassium, chloride) (**Figure 3**) [:ref:`5 `]. - -.. figure:: ../images/mousepad-old-solvent.png - :align: center - :width: 60% - - **Figure 3.** SIRAH force field Solvent CG representation. - -Unlike typical CG water, SIRAH's WatFour (WT4) model aimed to replicate the structure of an elementary water cluster, including a central water surrounded by four identical molecules forming a tetrahedron. Hydrogen atoms were removed, and only the oxygen atoms at the tetrahedron's vertices were retained, connected by harmonic bonds. This flexible tetrahedral structure generated its own dielectric permittivity and electrostatic screening by adding partial charges to the four beads, creating a quadrupole with two positively and two negatively charged beads. The partial charges were adopted from the SPC water model to ensure compatibility with fully atomistic water models for multiscale simulations [:ref:`5 `]. - -Iterative fitting was performed on the LJ energy well depth, which corresponded to the experimental diffusion coefficient of pure water at 300 K, and the bead size, which mirrored the second solvation peak of water. The mass of the beads was set to achieve a density of 1 kg/dl. The WT4 model, which resembled a bulkier "water molecule," corresponded to the second apex of the radial distribution function for atomistic water. - -Monovalent ions in SIRAH, represented by single beads with a net charge of +/- 1e, were developed based on neutron scattering data, reflecting the chemical identity of sodium, potassium, and chloride ions [:ref:`5 `]. The ions' depth of the LJ well matched that of the WT4 beads, offering the flexibility to adjust ionic strength by modifying added salt in the simulation box. The incorporation of electrolytic ions and accurate electrostatic description using the Particle Mesh Ewald summation methods contribute to the relevant features of SIRAH. - - -The CG protein model ---------------------- - -The CG protein model in SIRAH employs varying bead sizes to reflect different amino acid interactions. The latest version [:ref:`2 `], refined in 2019, has significantly improved the ability to reproduce protein structures. The atomistic to CG mapping of protein side chains follows the DNA model philosophy, with effective beads placed at selected atoms along side chains, representing hydrophobic, aromatic, and polar interactions (**Figure 4**). - -.. figure:: ../images/mousepad-old-amino.png - :align: center - :width: 90% - - **Figure 4.** SIRAH force field amino acids CG representation. - -Hydrophobic amino acids are neutral beads at specific positions with an LJ diameter of 0.42 nm. Aromatic amino acids use smaller beads, 0.35 nm, for stacking-like interactions, with partial charges on certain residues to preserve Hydrogen bond possibilities. Polar amino acids retain beads in functional groups, while acidic and basic amino acids have partial charges which add up to a net charge of +/- 1e. - -The aminoacidic backbone is represented with three beads for Nitrogen, Cα Carbon, and carboxylic Oxygen positions, facilitating easy transformation between all-atoms and CG. Bonded parameters for amino acids follow the rules outlined for DNA, with force constants for bond and angular stretching adapted from the same set of parameters. This approach has been found to be effective and time-efficient. - -In version 2.2 [:ref:`2 `], all bead masses are set to 50 a.u., and common post-translational modifications, including phosphorylation and acetylation, and different protonation states are available. In addition, divalent ion parameters for Zinc, Magnesium, and Calcium, derived from statistical analyses and validated through multiple CG simulations, enable SIRAH simulations of a wide range of metal-bound macromolecules. - - -CG models for phospholipids ---------------------------------------- - -Following the completion of DNA, aqueous solvent, and protein models, the SIRAH force field aimed to incorporate a suitable CG lipid representation for simulating membrane proteins. Focusing on prototypical phospholipids, including phosphatidyl-choline (PC), -ethanolamine (PE), and –serine (PS) heads, along with myristoyl (M), palmitic (P), and oleic (O) acyl chains, SIRAH enabled simulations of diverse eukaryotic membrane components [:ref:`6 `]. Utilizing the existing functional groups in the force field, parameterization of these lipids required minimal modifications, ensuring compatibility and accurate replication of lipid bilayer mechanical properties such as thickness, areas per lipid, order parameter, etc., and their dependence with the temperature. - -During protein simulations embedded in lipid bilayers, spurious insertions of acyclic tails into the protein core were observed. To address this, specific interactions between hydrophobic protein side chains and acyl chains were set outside Lorentz-Berthelot combination rules, yielding accurate representations of the SarcoEndoplasmic Reticulum Calcium (SERCA) pump's tilted orientation in a DMPC bilayer [:ref:`6 `]. This modification facilitated simulations of electrostatics-driven opening of Connexin 26 channels, demonstrating predictive power in identifying mutations inhibiting channel opening [:ref:`7 `]. The approach was also employed for cost-effective simulations of entire viral capsids and envelopes, allowing construction and simulation of a Zika Virus-Like Particles on a multi-microsecond time scale [:ref:`8 `]. - - -Multiscale simulations ------------------------ - -The development of the SIRAH force field in a classical two-body Hamiltonian framework has facilitated multiscale simulations, eliminating the need for non-Hamiltonian interaction terms and ensuring efficiency without communication delays between software modules. - -Two multiscale implementations in SIRAH are emphasized: first, an all-atoms/CG model covalently linking both resolutions within a nucleic acid chain [:ref:`9 `]; second, a multiresolution solvent model allowing the mixture of fully atomistic solutes with a shell of atomistic solvent surrounded by CG water, applicable to highly solvated systems like viral capsids [:ref:`10 `]. - -A triple solvation scheme, treating water at all-atoms, CG, and supraCG levels, is also available. This is particularly useful for complex cellular systems and has been applied to assemble and simulate VLPs systems in an onion-shaped configuration using CG water (WT4) and supra-CG solvent (WLS) [:ref:`10 `]. MD simulations of entire VLPs, such as those studying Flaviviruses with membranes and proteinaceous envelopes, offer crucial insights into their dynamics and are vital for understanding biological systems at a level accessible only through computer simulations [:ref:`8 `]. - - -Overwriting combination rules --------------------------------- - -The SIRAH force field introduces a modification in the calculation of LJ interactions to address issues with electrolytic ions in proteins and DNA. Unlike traditional MD packages using Lorentz-Berthelot (LB) combination rules, SIRAH employs an "outside-of-LB trick" that allows specific LJ parameters for certain bead pairs, enabling the fine-tuning of interactions. This approach provides adaptability to regulate interactions applying only to specific bead pairs, in accordance with various physicochemical settings [:ref:`3 `]. - -SIRAH comprises 56 different bead types, with 197 interactions defined outside LB combination rules among 1540 possible pair combinations [:ref:`3 `]. The modifications include cation-π interactions between aromatic residues and Lysine, methylated Lysine, and zwitterionic N-terminal beads. The force field corrects the size of backbone beads, crucial for forming α helices and Hydrogen bonds, ensuring compatibility with compact structures. It facilitates the formation of secondary structure elements and enhances interactions with other force field components. - - -Performance ------------- - -The latest version of the SIRAH force field leverages GPU implementations in GROMACS and AMBER, enabling CG simulations on desktop computers at a rate of a few microseconds per day for medium-sized systems. Larger systems of around a million particles can achieve speeds of hundreds of nanoseconds per day [:ref:`2 `]. - -Recently, to illustrate SIRAH's performance, a comparison was made between a SIRAH CG simulation and an atomistic simulation (Amber's FF14SB) of the SARS-CoV-2 Spike protein's receptor binding domain (RBD) with human ACE2 and the amino acid transporter B0AT1 (see [:ref:`3 `]). The CG model exhibited a 60-fold speedup, simulating approximately 660 ns per day with a 20 fs time step, compared to the atomistic model's 11 ns per day with a 2 fs time step, using the same system. - -Nevertheless, it is essential to take into account the constraints of the force field beyond its speed implications, as various force fields may possess distinct capabilities. Thus, exercise caution when making direct comparisons between CG force fields, considering their distinct strengths and drawbacks. - - -Limitations ------------- - -Although the SIRAH force field offers speed, efficiency, and multiscale capabilities for simulating biomolecular systems, it has some limitations such as: - -* It potentially compromises precision in both structural and energetic aspects. SIRAH, similar to other CG force fields, faces limitations in scenarios that demand atomic-level precision, such as interactions mediated by single water molecules or ligands with specific binding sites. Examples like potassium channels or aquaporins, where individual water molecules play a crucial role, may be challenging for CG models that combine multiple water molecules into a single effective bead. - -* Protein folding simulations are not extensively explored. Although SIRAH is successful in reproducing spontaneous aggregation and small peptide folding, the unbiased formation of large helical segments remains challenging. - -* The molecular diversity in biological systems is vast, making it nearly impossible to encompass all relevant biomolecules. Establishing a generally valid methodology for creating arbitrary molecular topologies involves converting new topologies from all-atom to CG, relying on experimental data, organic chemistry knowledge, and physicochemical intuition. - - -Perspectives -------------- - -The rapid advancement of computer power has established MD as a valuable tool in biomedical sciences for understanding intricate processes and vast biological systems. Developing force fields that are universally applicable to all biological molecular families and enable communication at different levels of molecular resolution is a crucial and complex task. Recently, the SIRAH force field expanded its scope by incorporating glycans to simulate polysaccharide chains and protein glycosylation (see [:ref:`11 `]). In addition, the lipid diversity will be enhanced by including sphingomyelins, ceramides, and cholesterol, crucial components of endoplasmic reticulum membranes and flaviviral envelopes. Additionally, testing parameters for POPG, a lipid found in bacterial membranes, is underway to improve the realism of antibiotic peptide mode of action descriptions. In the medium term, there are plans to introduce a coarse-grained model for RNA, which is crucial for the description of viral particles and a major area of focus for the group's ongoing research. - - -References -------------- - -.. _ref1: - -[1] Borges-Araújo, L.; Patmanidis, I.; Singh, A. P.; Santos, L. H. S.; Sieradzan, A. K.; Vanni, S.; Czaplewski, C.; Pantano, S.; Wataru Shinoda, W.; Monticelli, L.; Liwo, A.; Marrink, S. J.; Souza, P. C. T. 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Journal of Chemical Theory and Computation 2010, 6, 1711–1725. |DNA| |DNA-cit| - -.. |DNA| image:: https://img.shields.io/badge/DOI-10.1021%2Fct900653p-blue - :alt: Access the paper - :target: https://doi.org/10.1021/ct900653p - -.. |DNA-cit| image:: https://img.shields.io/endpoint?url=https%3A%2F%2Fapi.juleskreuer.eu%2Fcitation-badge.php%3Fshield%26doi%3D10.1021%2Fct900653p - :alt: Citation - :target: https://scholar.google.com/scholar?oi=bibs&hl=es&cites=12499613729973955498 - -.. _ref5: - -[5] Darré, L.; Machado, M. R.; Dans, P. D.; Herrera, F. E.; Pantano, S. Another Coarse Grain Model for Aqueous Solvation: WAT FOUR? 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Journal of Chemical Theory and Computation 2017, 13, 5106–5116. |MC1| |MC1-cit| - -.. |MC1| image:: https://img.shields.io/badge/DOI-10.1021%2Facs.jctc.7b00659-blue - :alt: Access the paper - :target: https://doi.org/10.1021/acs.jctc.7b00659 - -.. |MC1-cit| image:: https://img.shields.io/endpoint?url=https%3A%2F%2Fapi.juleskreuer.eu%2Fcitation-badge.php%3Fshield%26doi%3D10.1021%2Facs.jctc.7b00659 - :alt: Citation - :target: https://scholar.google.com/scholar?cites=16637391138490147245 - -.. _ref11: - -[11] Garay, P. G.; Machado, M. R.; Verli, H.; Pantano, S. SIRAH late harvest: coarse-grained models for protein glycosylation. Journal of Chemical Theory and Computation 2024. |GLY| |GLY-cit| - -.. |GLY| image:: https://img.shields.io/badge/DOI-10.1021%2Facs.jctc.3c00783-blue - :alt: Access the paper - :target: https://pubs.acs.org/doi/10.1021/acs.jctc.3c00783 - -.. |GLY-cit| image:: https://img.shields.io/endpoint?url=https%3A%2F%2Fapi.juleskreuer.eu%2Fcitation-badge.php%3Fshield%26doi%3D10.1021%2Facs.jctc.3c00783 - :alt: Citation diff --git a/docs/source/GROMACS/Tutorial-1.rst b/docs/source/GROMACS/Tutorial-1.rst index 1f3393e..442d3d4 100644 --- a/docs/source/GROMACS/Tutorial-1.rst +++ b/docs/source/GROMACS/Tutorial-1.rst @@ -83,7 +83,7 @@ these restraints edit ``topol.top`` to include the file ``WC_RST.itp`` at the en - Topology with WC restraints * - | ; Include Position restraint file | #ifdef POSRES - | #include "posre.itp" + | #include \"posre.itp\" | #endif | | @@ -91,11 +91,11 @@ these restraints edit ``topol.top`` to include the file ``WC_RST.itp`` at the en - | ; Include Position restraint file | #ifdef POSRES - | #include "posre.itp" + | #include \"posre.itp\" | #endif | | ; Watson-Crick restraints - | #include "./sirah.ff/tutorial/1/WC_RST.itp" + | #include \"./sirah.ff/tutorial/1/WC_RST.itp\" 1.3. Solvate the system diff --git a/docs/source/GROMACS/Tutorial-2.rst b/docs/source/GROMACS/Tutorial-2.rst index d87f740..6ea7e0f 100644 --- a/docs/source/GROMACS/Tutorial-2.rst +++ b/docs/source/GROMACS/Tutorial-2.rst @@ -36,14 +36,14 @@ For GROMACS to recognize SIRAH, edit your topology file ``topol.top`` adding the * - Topology before editing - Topology after editing * - | ; Include forcefield parameters - | #include “amber99sb.ff/forcefield.itp” + | #include \"amber99sb.ff/forcefield.itp\" | | - | ; Include forcefield parameters - | #include “amber99sb.ff/forcefield.itp” - | #include “./sirah.ff/hybsol_comb2.itp” - | #include “./sirah.ff/solv.itp” + | #include \"amber99sb.ff/forcefield.itp\" + | #include \"./sirah.ff/hybsol_comb2.itp\" + | #include \"./sirah.ff/solv.itp\" .. important:: diff --git a/docs/source/GROMACS/Tutorial-3.rst b/docs/source/GROMACS/Tutorial-3.rst index 5370681..c4d1832 100644 --- a/docs/source/GROMACS/Tutorial-3.rst +++ b/docs/source/GROMACS/Tutorial-3.rst @@ -234,7 +234,7 @@ Add the restraints to ``topol.top``: - Topology after editing * - | ; Include Position restraint file | #ifdef POSRES - | #include "posre.itp" + | #include \"posre.itp\" | #endif | @@ -250,17 +250,17 @@ Add the restraints to ``topol.top``: - | ; Include Position restraint file | #ifdef POSRES - | #include "posre.itp" + | #include \"posre.itp\" | #endif | ; Backbone restraints | #ifdef GN_GO - | #include "bkbres.itp" + | #include \"bkbres.itp\" | #endif | ; Backbone soft restrains | #ifdef GN_GO_SOFT - | #include "bkbres_soft.itp" + | #include \"bkbres_soft.itp\" | #endif 3.4. Run the simulation @@ -359,79 +359,3 @@ Now you can check the simulation using VMD: The file ``sirah_vmdtk.tcl`` is a Tcl script that is part of SIRAH Tools and contains the macros to properly visualize the coarse-grained structures in VMD. Use the command ``sirah-help`` in the Tcl/Tk console of VMD to access the manual pages. To learn about SIRAH Tools' capabilities, you can also go to the :ref:`SIRAH Tools tutorial `. -3.6. Calculate the solvent accessible surface (SAS) -____________________________________________________ - -Create the following symbolic link in the folder ``run/``: - -.. code-block:: bash - - ln -s ../sirah.ff/vdwradii.dat - -Calculate the SAS of the protein along the trajectory: - -.. code-block:: bash - - g_sas -s 1CRN_cg_md.tpr -f 1CRN_cg_md_pbc.xtc -n ../1CRN_cg_ion.ndx -qmax 0 -probe 0.21 -o area.xvg - -When prompted, choose *Protein* as both the group for calculation and the output. - -.. note:: - - The solvent probe radius corresponds to a WT4 bead while a charge of 0e refers to any - hydrophobic bead. The file ``vdwradii.dat`` must be placed at the same folder where *gmx sasa* is executed to assure that the correct van der Waals radii of SIRAH beads are used in the calculation. - -.. important:: - - *g_sas* is deprecated, the tool no longer automatically divides the surface into hydrophobic and hydrophilic areas, and there is no ``-f_index`` option. The same effects can be obtained by defining suitable selections for ``-output``. If you want output that contains the same numbers as with the old tool for a calculation group A and output group B, you can use `[1] `_. :: - - gmx sasa -surface 'group "A"' -output '"Hydrophobic" group "A" and charge {-0.2 to 0.2}; "Hydrophilic" group "B" and not charge {-0.2 to 0.2}; "Total" group "B"' - - -Use Xmgrace to plot the results: - -.. code-block:: bash - - xmgrace -nxy area.xvg - -.. - 3.7. Visualize the secondary structure - ________________________________________ - - - Load the processed trajectory in VMD:: - - vmd ../1CRN_cg_ion.psf ../1CRN_cg_ion.gro 1CRN_cg_md_pbc.xtc -e ../sirah.ff/tools/sirah_vmdtk.tcl - - .. note:: - - The file ``sirah_vmdtk.tcl`` is a Tcl script that is part of SIRAH Tools and contains the macros to properly visualize the coarse-grained structures in VMD. Use the command ``sirah-help`` in the Tcl/Tk console of VMD to access the manual pages. To learn about SIRAH Tools' capabilities, you can also go to the :ref:`SIRAH Tools tutorial `. - - At the *Tk/Tcl console* run the command ``sirah_ss`` to get the secondary structure of the CG protein. - - .. note:: - - After assigning the secondary structure it is possible to represent a-helices with Bendix in VMD - 1.9.2 or upper by setting the backbone particle name to GC (do not check the CG box). - - To analyze the output files from ``sirah_ss``, go back at the shell command line and execute:: - - xmgrace -nxy ss_by_frame.xvg - - .. code-block:: bash - - xmgrace -nxy ss_by_res.xvg - - The file ss.mtx can be processed to visualize the time evolution of the secondary structure by residue:: - - ../sirah.ff/tools/ssmtx2png.R --mtx=ss.mtx - - .. code-block:: bash - - display ssmtx.png - - .. hint:: - - The usage of ssmtx2png.R can be accessed through:: - - ../sirah.ff/tools/ssmtx2png.R --help diff --git a/docs/source/GROMACS/Tutorial-6.rst b/docs/source/GROMACS/Tutorial-6.rst index a5f9ae1..4db4696 100644 --- a/docs/source/GROMACS/Tutorial-6.rst +++ b/docs/source/GROMACS/Tutorial-6.rst @@ -343,7 +343,7 @@ Edit each ``topol_Protein_chain_*.itp`` (A to E) to include the new position res - Topology after editing * - | ; Include Position restraint file | #ifdef POSRES - | #include "posre_Protein.itp" + | #include \"posre_Protein.itp\" | #endif | | @@ -352,11 +352,11 @@ Edit each ``topol_Protein_chain_*.itp`` (A to E) to include the new position res - | ; Include Position restraint file | #ifdef POSRES - | #include "posre_Protein.itp" + | #include \"posre_Protein.itp\" | #endif | | #ifdef POSREBB - | #include "posre_BB.itp" + | #include \"posre_BB.itp\" | #endif Use a similar procedure to set the positional restraints on lipid's phosphates. @@ -392,7 +392,7 @@ Edit ``topol_Lipid_chain_F.itp`` to include the new position restraints and defi - Topology after editing * - | ; Include Position restraint file | #ifdef POSRES - | #include "posre_Lipid_chain_F.itp" + | #include \"posre_Lipid_chain_F.itp\" | #endif | | @@ -401,11 +401,11 @@ Edit ``topol_Lipid_chain_F.itp`` to include the new position restraints and defi - | ; Include Position restraint file | #ifdef POSRES - | #include "posre_Lipid_chain_F.itp" + | #include \"posre_Lipid_chain_F.itp\" | #endif | | #ifdef POSREZ - | #include "posre_Pz.itp" + | #include \"posre_Pz.itp\" | #endif 6.5. Run the simulation diff --git a/docs/source/GROMACS/Tutorial-7.rst b/docs/source/GROMACS/Tutorial-7.rst index 258073f..7a5341c 100644 --- a/docs/source/GROMACS/Tutorial-7.rst +++ b/docs/source/GROMACS/Tutorial-7.rst @@ -8,12 +8,11 @@ This tutorial shows how to apply the multiscale solvation approach of SIRAH forc We strongly advise you to read and complete :ref:`Tutorial 2 ` and :ref:`Tutorial 3 ` before starting. We also recommend you to perform the `Umbrella Sampling `__ tutorial of GROMACS to get familiar with pulling simulations parameters. - .. important:: Check the :ref:`Setting up SIRAH ` section for download and set up details before starting this tutorial. Since this is **Tutorial 7**, remember to replace ``X.X``, the files corresponding to this tutorial can be found in: ``sirah.ff/tutorial/7/`` - + 7.1. Setting pulling direction ________________________________ @@ -65,7 +64,12 @@ ______________________________ Other option is the `PDB2PQR server `_ and choosing the output naming scheme of AMBER for best compatibility. This server was utilized to generate the *PQR* file featured in this tutorial. Be aware that modified residues lacking parameters such as: MSE (seleno MET), TPO (phosphorylated THY), SEP (phosphorylated SER) or others are deleted from the PQR file by the server. In that case, mutate the residues to their unmodified form before submitting the structure to the server. See :ref:`Tutorial 3 ` for cautions while preparing and mapping atomistic proteins to SIRAH. - + +.. important:: + + Check the :ref:`Setting up SIRAH ` section for download and set up details before starting this tutorial. + Since this is **Tutorial 7**, remember to replace ``X.X``, the files corresponding to this tutorial can be found in: ``sirah.ff/tutorial/7/`` + Map the atomistic structure of the I10 domain to its CG representation: .. code-block:: bash @@ -106,7 +110,7 @@ In this specific case, the charge of the system is -5.000 e; this will be addres .. note:: - By default charged terminal are used but it is possible to set them neutral with option ``-ter`` + By default charged terminal are used but it is possible to set them neutral with option ``-ter``. .. note:: @@ -128,15 +132,15 @@ _______________________ In this system, I10 has 88 amino acids and the maximum extension size of each amino acid is 0.34 nm. Thus, "stretched" protein will be 88 * 0.34 = 29.92 nm (~ 30.0 nm) long. In order to accommodate the pulling, GROMACS stipulates a minimum box size double this value, i.e. 60 nm for the Z-axis. However, for optimal results, it is recommended that the dimensions of the box be 2.5 to 3 times greater than the maximum length of the protein when in its extended conformation. Therefore, for this tutorial the box used is 10 10 90 nm. - .. figure:: /../images/TutorialSMD2.png + .. figure:: /../images/TutorialSMD2_1.png :align: center :width: 100% **Figure 2.** Dimensions of the multiscale solvation box used in this tutorial. -In order to have a multiscale solvent approach using WT4 and WLS, two steps are needed to solvate the systems. +In order to have a multiscale solvent approach using WT4 (CG solvent) and WLS (Supra-CG solvent), two steps are needed to solvate the systems. -First, define the simulation region of the system to be enclosed by WT4 (pink in **Figure 2**) +First, define the simulation region of the system to be enclosed by WT4 (purple in **Figure 2**) .. code-block:: bash @@ -178,7 +182,7 @@ Edit the [ molecules ] section in ``topol.top`` to include the number of added W .. hint:: - If you forget to read the number of added WT4 molecules from the output of *solvate*, then use the following command line to get it + If you forget to read the number of added WT4 molecules from the output of *solvate*, then use the following command line to get it: .. code-block:: console @@ -192,30 +196,30 @@ Remove misplaced WT4 molecules within 0.3 nm of protein: .. code-block:: bash - echo q | gmx make_ndx -f I10_cg_sol1.gro -o I10_cg_sol1.ndx + echo q | gmx make_ndx -f I10_cg_solv1.gro -o I10_cg_solv1.ndx .. code-block:: bash - gmx grompp -f sirah.ff/tutorial/7/GPU/em1_CGPROT.mdp -p topol.top -po delete1.mdp -c I10_cg_sol1.gro -o I10_cg_sol1.tpr -maxwarn 2 + gmx grompp -f sirah.ff/tutorial/7/em1_CGPROT.mdp -p topol.top -po delete1.mdp -c I10_cg_solv1.gro -o I10_cg_solv1.tpr -maxwarn 2 .. caution:: - New GROMACS versions may complain about the non-neutral charge of the system, aborting the generation of the TPR file by command grompp. We will neutralize the system later, so to overcame this issue, just allow warning messages by adding the following keyword to the grompp command line: ``-maxwarn 2`` + New GROMACS versions may complain about not used macros and the non-neutral charge of the system, aborting the generation of the TPR file by command grompp. We will neutralize the system later, so to overcame these issues, just allow warning messages by adding the following keyword to the grompp command line: ``-maxwarn 2`` .. code-block:: bash - gmx select -f I10_cg_sol1.gro -s I10_cg_sol1.tpr -n I10_cg_sol1.ndx -on rm_close_wt4.ndx -select 'not (same residue as (resname WT4 and within 0.3 of group Protein))' + gmx select -f I10_cg_solv1.gro -s I10_cg_solv1.tpr -n I10_cg_solv1.ndx -on rm_close_wt4.ndx -select 'not (same residue as (resname WT4 and within 0.3 of group Protein))' .. code-block:: bash - gmx editconf -f I10_cg_sol1.gro -o I10_cg_sol2.gro -n rm_close_wt4.ndx + gmx editconf -f I10_cg_solv1.gro -o I10_cg_solv2.gro -n rm_close_wt4.ndx Edit the [ molecules ] section in ``topol.top`` to correct the number of WT4 molecules, **6261**. .. hint:: - If you forget to read the number of added WT4 molecules from the output of *solvate*, then use the following command line to get it + If you forget to read the number of added WT4 molecules from the output of *solvate*, then use the following command line to get it: .. code-block:: console @@ -226,7 +230,7 @@ Now, we include the second solvent layer of solvent with WLS molecules (green in .. code-block:: bash - gmx editconf -f I10_cg_sol2.gro -o I10_cg_box2.gro -box 10 10 90 -bt triclinic -c + gmx editconf -f I10_cg_solv2.gro -o I10_cg_box2.gro -box 10 10 90 -bt triclinic -c .. hint:: @@ -247,7 +251,7 @@ Add WLS molecules: .. code-block:: bash - gmx solvate -cp I10_cg_box2.gro -cs sirah.ff/wlsbox.gro -o I10_cg_sol3.gro + gmx solvate -cp I10_cg_box2.gro -cs sirah.ff/wlsbox.gro -o I10_cg_solv3.gro .. note:: @@ -278,7 +282,7 @@ Edit the [ molecules ] section in ``topol.top`` to include the number of added W .. hint:: - If you forget to read the number of added WLS molecules from the output of *solvate*, then use the following command line to get it + If you forget to read the number of added WLS molecules from the output of *solvate*, then use the following command line to get it: .. code-block:: console @@ -292,25 +296,25 @@ Remove misplaced WLS molecules within 7.8 nm of protein: .. code-block:: bash - echo q | gmx make_ndx -f I10_cg_sol3.gro -o I10_cg_sol3.ndx + echo q | gmx make_ndx -f I10_cg_solv3.gro -o I10_cg_solv3.ndx .. code-block:: bash - gmx grompp -f sirah.ff/tutorial/7/GPU/em1_CGPROT.mdp -p topol.top -po delete3.mdp -c I10_cg_sol3.gro -o I10_cg_sol3.tpr -maxwarn 2 + gmx grompp -f sirah.ff/tutorial/7/em1_CGPROT.mdp -p topol.top -po delete3.mdp -c I10_cg_solv3.gro -o I10_cg_solv3.tpr -maxwarn 2 .. caution:: - New GROMACS versions may complain about the non-neutral charge of the system, aborting the generation of the TPR file by command grompp. We will neutralize the system later, so to overcame this issue, just allow warning messages by adding the following keyword to the grompp command line: ``-maxwarn 2`` + New GROMACS versions may complain about not used macros and the non-neutral charge of the system, aborting the generation of the TPR file by command grompp. We will neutralize the system later, so to overcame this issue, just allow warning messages by adding the following keyword to the grompp command line: ``-maxwarn 2`` .. code-block:: bash - gmx select -f I10_cg_sol3.gro -s I10_cg_sol3.tpr -n I10_cg_sol3.ndx -on rm_close_wls.ndx -select 'not (same residue as (resname WLS and within 7.8 of group Protein))' + gmx select -f I10_cg_solv3.gro -s I10_cg_solv3.tpr -n I10_cg_solv3.ndx -on rm_close_wls.ndx -select 'not (same residue as (resname WLS and within 7.8 of group Protein))' .. code-block:: bash - gmx editconf -f I10_cg_sol3.gro -o I10_cg_sol4.gro -n rm_close_wls.ndx + gmx editconf -f I10_cg_solv3.gro -o I10_cg_solv4.gro -n rm_close_wls.ndx -Edit the [ molecules ] section in ``topol.top`` to correct the number of WLS molecules, **4582**. +Edit the [ molecules ] section in ``topol.top`` to correct the number of WLS molecules, **4580**. .. hint:: @@ -330,15 +334,15 @@ Add CG counterions and 0.15M NaCl: .. code-block:: bash - gmx grompp -f sirah.ff/tutorial/7/GPU/em1_CGPROT.mdp -p topol.top -po delete4.mdp -c I10_cg_sol4.gro -o I10_cg_sol4.tpr -maxwarn 3 + gmx grompp -f sirah.ff/tutorial/7/em1_CGPROT.mdp -p topol.top -po delete4.mdp -c I10_cg_solv4.gro -o I10_cg_solv4.tpr -maxwarn 2 .. caution:: - New GROMACS versions may complain about the non-neutral charge of the system, aborting the generation of the TPR file by command grompp. We are about to neutralize the system, so to overcame this issue, just allow warning messages by adding the following keyword to the grompp command line: ``-maxwarn 3`` + New GROMACS versions may complain about not used macros and the non-neutral charge of the system, aborting the generation of the TPR file by command grompp. We are about to neutralize the system, so to overcame this issue, just allow warning messages by adding the following keyword to the grompp command line: ``-maxwarn 2`` .. code-block:: bash - gmx genion -s I10_cg_sol4.tpr -o I10_cg_ion.gro -np 187 -pname NaW -nn 182 -nname ClW + gmx genion -s I10_cg_solv4.tpr -o I10_cg_ion.gro -np 189 -pname NaW -nn 184 -nname ClW When prompted, choose to substitute *WT4* molecules by *ions*. @@ -367,10 +371,10 @@ Edit the [ molecules ] section in ``topol.top`` to include the CG ions and the c - | [ molecules ] | ; Compound #mols | Protein_chain_A 1 - | WT4 5892 - | NaW 187 - | ClW 182 - | WLS 4582 + | WT4 5888 + | NaW 189 + | ClW 184 + | WLS 4580 .. caution:: @@ -422,11 +426,13 @@ Generate restraint files for the backbone *GN* and *GO* beads: gmx genrestr -f I10_cg.gro -n I10_cg_ion.ndx -o bkbres.itp +When prompted, choose the group *GN_GO*. + .. code-block:: bash gmx genrestr -f I10_cg.gro -n I10_cg_ion.ndx -o bkbres_soft.itp -fc 100 100 100 -When prompted, choose the group *GN_GO* +Here, choose the group *GN_GO*. Add the restraints to ``topol.top``: @@ -439,11 +445,11 @@ Add the restraints to ``topol.top``: - Topology after editing * - | ; Include Position restraint file | #ifdef POSRES - | #include "posre.itp" + | #include \"posre.itp\" | #endif | ; Include water topology - | #include"../sirah.ff/solv.itp" + | #include \"../sirah.ff/solv.itp\" | | #ifdef POSRES_WATER @@ -463,29 +469,24 @@ Add the restraints to ``topol.top``: | | - | - | - | - | - - + - | ; Include Position restraint file | #ifdef POSRES - | #include "posre.itp" + | #include \"posre.itp\" | #endif | ; Backbone restraints | #ifdef GN_GO - | #include "bkbres.itp" + | #include \"bkbres.itp\" | #endif | ; Backbone soft restrains | #ifdef GN_GO_SOFT - | #include "bkbres_soft.itp" + | #include \"bkbres_soft.itp\" | #endif | ; Include water topology - | #include"../sirah.ff/solv.itp" + | #include \"../sirah.ff/solv.itp\" | #ifdef POSRES_WATER | ; Position restraint for each water oxygen @@ -493,12 +494,8 @@ Add the restraints to ``topol.top``: | ; i funct fcx fcy fcz | 1 1 1000 1000 1000 | #endif + | - | ; Solvent restrains - | #ifdef Sirah_solvent - | #include "posre_sirah_solvent.itp" - | #endif - | 7.5. Run the simulation @@ -506,9 +503,9 @@ ________________________ .. important:: - By default in this tutorial we will use input files for GROMACS on GPU (``sirah.ff/tutorial/7/GPU``). + By default in this tutorial we will use input files for GROMACS on GPU (``sirah.ff/tutorial/7/``). -The folder ``sirah.ff/tutorial/7/GPU/`` contains typical input files for energy minimization (``em1_CGPROT.mdp``, ``em2_CGPROT.mdp``, and ``em3_CGPROT.mdp``), equilibration (``eq1_CGPROT.mdp`` and ``eq2_CGPROT.mdp``), production (``md_CGPROT.mdp``) and SMD (``SMD_Force_CGPROT.mdp`` and ``SMD_Velocity_CGPROT.mdp``) runs. Please check carefully the input flags therein. +The folder ``sirah.ff/tutorial/7/`` contains typical input files for energy minimization (``em1_CGPROT.mdp``, ``em2_CGPROT.mdp``, and ``em3_CGPROT.mdp``), equilibration (``eq1_CGPROT.mdp`` and ``eq2_CGPROT.mdp``), production (``md_CGPROT.mdp``) and SMD (``SMD_Force_CGPROT.mdp`` and ``SMD_Velocity_CGPROT.mdp``) runs. Please check carefully the input flags therein. Make a new folder for the run: @@ -516,11 +513,11 @@ Make a new folder for the run: mkdir run; cd run -**Energy Minimization of side chains by restraining the backbone and Sirah-solvent**: +**Energy Minimization of side chains and Sirah-solvent by restraining the backbone**: .. code-block:: bash - gmx grompp -f ../sirah.ff/tutorial/7/GPU/em1_CGPROT.mdp -p ../topol.top -po em1.mdp -n ../I10_cg_ion.ndx -c ../I10_cg_ion.gro -r ../I10_cg_ion.gro -o I10_cg_em1.tpr + gmx grompp -f ../sirah.ff/tutorial/7/em1_CGPROT.mdp -p ../topol.top -po em1.mdp -n ../I10_cg_ion.ndx -c ../I10_cg_ion.gro -r ../I10_cg_ion.gro -o I10_cg_em1.tpr .. code-block:: bash @@ -530,7 +527,7 @@ Make a new folder for the run: .. code-block:: bash - gmx grompp -f ../sirah.ff/tutorial/7/GPU/em2_CGPROT.mdp -p ../topol.top -po em2.mdp -n ../I10_cg_ion.ndx -c I10_cg_em1.gro -o I10_cg_em2.tpr + gmx grompp -f ../sirah.ff/tutorial/7/em2_CGPROT.mdp -p ../topol.top -po em2.mdp -n ../I10_cg_ion.ndx -c I10_cg_em1.gro -r I10_cg_em1.gro -o I10_cg_em2.tpr .. code-block:: bash @@ -540,7 +537,7 @@ Make a new folder for the run: .. code-block:: bash - gmx grompp -f ../sirah.ff/tutorial/7/GPU/em3_CGPROT.mdp -p ../topol.top -po em3.mdp -n ../I10_cg_ion.ndx -c I10_cg_em2.gro -o I10_cg_em3.tpr + gmx grompp -f ../sirah.ff/tutorial/7/em3_CGPROT.mdp -p ../topol.top -po em3.mdp -n ../I10_cg_ion.ndx -c I10_cg_em2.gro -o I10_cg_em3.tpr .. code-block:: bash @@ -550,7 +547,7 @@ Make a new folder for the run: .. code-block:: bash - gmx grompp -f ../sirah.ff/tutorial/7/GPU/eq1_CGPROT.mdp -p ../topol.top -po eq1.mdp -n ./I10_cg_ion.ndx -c I10_cg_em2.gro -r I10_cg_em2.gro -o I10_cg_eq1.tpr + gmx grompp -f ../sirah.ff/tutorial/7/eq1_CGPROT.mdp -p ../topol.top -po eq1.mdp -n ../I10_cg_ion.ndx -c I10_cg_em2.gro -r I10_cg_em2.gro -o I10_cg_eq1.tpr .. code-block:: bash @@ -560,7 +557,7 @@ Make a new folder for the run: .. code-block:: bash - gmx grompp -f ../sirah.ff/tutorial/7/GPU/eq2_CGPROT.mdp -p ../topol.top -po eq2.mdp -n ../I10_cg_ion.ndx -c I10_cg_eq1.gro -r I10_cg_eq1.gro -o I10_cg_eq2.tpr + gmx grompp -f ../sirah.ff/tutorial/7/eq2_CGPROT.mdp -p ../topol.top -po eq2.mdp -n ../I10_cg_ion.ndx -c I10_cg_eq1.gro -r I10_cg_eq1.gro -o I10_cg_eq2.tpr .. code-block:: bash @@ -592,7 +589,7 @@ In this tutorial we are going to run only the **SMD Force** simulation: .. code-block:: bash - gmx grompp -f ../sirah.ff/tutorial/7/GPU/SMD_Force_CGPROT.mdp -p ../topol.top -po md.mdp -n ../I10_cg_ion_pull.ndx -c I10_cg_eq2.gro -o I10_cg_SMD_F.tpr + gmx grompp -f ../sirah.ff/tutorial/7/SMD_Force_CGPROT.mdp -p ../topol.top -po md.mdp -n ../I10_cg_ion_pull.ndx -c I10_cg_eq2.gro -o I10_cg_SMD_F.tpr .. code-block:: bash @@ -602,7 +599,7 @@ However, you can also run a **SMD Velocity** simulation: .. code-block:: bash - gmx grompp -f ../sirah.ff/tutorial/7/GPU/SMD_Velocity_CGPROT.mdp -p ../topol.top -po md.mdp -n ../I10_cg_ion_pull.ndx -c I10_cg_eq2.gro -o I10_cg_SMD_V.tpr + gmx grompp -f ../sirah.ff/tutorial/7/SMD_Velocity_CGPROT.mdp -p ../topol.top -po md.mdp -n ../I10_cg_ion_pull.ndx -c I10_cg_eq2.gro -o I10_cg_SMD_V.tpr .. code-block:: bash @@ -616,7 +613,7 @@ However, you can also run a **SMD Velocity** simulation: .. code-block:: bash - gmx grompp -f ../sirah.ff/tutorial/7/GPU/md_CGPROT.mdp -p ../topol.top -po md.mdp -n ../I10_cg_ion.ndx -c I10_cg_eq2.gro -o I10_cg_md.tpr + gmx grompp -f ../sirah.ff/tutorial/7/md_CGPROT.mdp -p ../topol.top -po md.mdp -n ../I10_cg_ion.ndx -c I10_cg_eq2.gro -o I10_cg_md.tpr .. code-block:: bash