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5

Atom reordering is a common problem in compchemistry. Rdkit (a python package) can do this, but it is limited by the formats it can read and mol2 files are a bit hit or miss. It works really well with SMILES, SMARTS and mol (sdf) files. But the writing may cause problems with Brookhaven pdb and mol2 files. So the formats you have are both problematic. One ...


5

TL;DR: docking is much slower than any ML approach, but the ML approach can be constrained by pharmacophores dictated by the active site. Side note: Scale The scale for ligand space exploration is generally is generally several orders of magnitude higher than "hundreds": Zinc DB lists 750 million enumerated compounds, GDB13 has enumerate all possible ...


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With pymol as a python module (conda install -c schrodinger pymol, not the GUI one), it is very easy. import pymol2 with pymol2.PyMOL() as pymol: pymol.cmd.load('protein.pdbqt', 'protein') # the second is the name within pymol instance. pymol.cmd.load('ligand.sdf', 'ligand') pymol.cmd.save('neighbours.pdb','ligand expand 3') # get atoms 3 Å ...


4

It's case specific Docking small compounds well is problematic and you need to consider whether: if a single conformer is okay if rigid sidechains are okay if implicit water is okay if a non-polarisable model is okay if a non-covalent interaction is okay if you are okay with a score that is a rough ΔΔGibbs approximation of the interaction (see this SO ...


3

It is utterly arbitrary and depends on your resources. We can all agree your cutoff would be a lot lower during the ordering step than at followup in silico analyses, but even then if you were ordering the top N at \$100-250 each, should you spend \$1,000 or \$10,000? In the in silico step you have real time and CPU-time to factor in making this call even ...


3

I'm not sure what you meant but you can take a look at NPDock (disclaimer we wrote that tool). If you have a structure of your protein of interest, you can dock it to the structure of your DNA/RNA of interest. Mind that this is a rigid body docking which means that the structure will not change upon binding.


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Hydrogens Most crystallographic structures are X-ray and the hydrogens are absent. In the case of neutron diffraction models, there may be many missing high b-factor ones (example in PDB:5MOP). As a consequence models are reprotonated. Also missing carbons and missing loop residues are added for some in silico applications too (not docking). However, it is ...


3

My answer is mainly based on molecular dynamics,but in this context it shouldn't make much of a difference. The main reason has to do with the force-field-water model used during the simulation. Examples of water models are SPC, TIP3P or TIP4P; same molecule (water) but different topology. A pdb usually comes from different sources and it can contain ...


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Autodock-Vina is a free molecular docking solution. You need to generate different input conformations for each ligand though, e.g. with RDKit. Here is a link to tutorial


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You can run a Molecular Dynamics simulation to see if the pose is stable and whether the protein changes/adapts it’s conformation. You can calculate the ligand efficiency, the docking score divided by the number if heavy atoms, and rank the compounds accordingly. You can also compare the scores of known ligands to the experimental values and see if the ...


2

There are a few steps in between pdb and .maps.fld. Here is the list of several scripts that can do tasks for you that you downloaded with autodock MGLTools: http://autodock.scripps.edu/faqs-help/faq/where-can-i-find-the-python-scripts-for-preparing-and-analysing-autodock-dockings. Look at the prepare_ files. Also note that the scripts come with a pre-...


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I don't think it is possible just from the docking scores. Docking scores are designed to give you an estimate of the binding affinity (entalphy), but they do not take entropic contributions into account very well. The best you can do are molecular dynamics simulations to calculate the free energy of binding. Which can be computationally quite costly e.g. ...


2

In general Most if not all docking applications will tolerate a jump. Furthermore, you really don't want to dock anything to the flexible regions even if you are using a program that does properly protein flexibility. Furthermore, if your protein adopts a closed conformation upon native substrate binding (not really the case here), you should start with that ...


2

An ent file is a pdb file. Just change the extension. PDBe for example provides their PDB files as such.


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Yes, if you are using implicit solvent you ought to remove all of them. Exception. Unless the crystallographic waters are trapped essential structural components of your active site and your ligand is not going to replace it, in which case keep it because its remove changes the energy of the active site —say you have a catalytic triad, with a water that is ...


2

Vina uses a non-deterministic docking algorithm. See the manual. The docking algorithm is non-deterministic. Even though with this receptor-ligand pair, the minimum of the scoring function corresponds to the correct conformation, the docking algorithm sometimes fails to find it. Try several times and see for yourself. Note that the probability of failing to ...


2

The difference between different force-fields is not going to be major, it is the side steps which are. When If you are starting from a SMILES string, optimisation is a must obviously. If you are using a 3D conformer from PubChem or even an actual sub-1 Å crystal structure from CSD, optimisation is nice for consistency. Which MMF94 is a solid choice. ...


2

It is best to contextualise the numbers. -1 kcal/mol is about the potential energy gained from a hydrogen bond —technically described in the r^6 part of the Lenard–Jones term, it is also the average collision energy of a water molecule at 37°C as that is RT ($\frac{k_b\cdot T}{N_A}$, wiki)under a Maxwell–Boltzmann distribution. A salt bridge –2 kcal/mol (...


2

I believe PDB2PQR CLI will do the work wonderfully. Don't let the name trick you: PQR files are organized like PDB ones. Under the hood it runs propka, which is state-of-the-art for predicting a protein residues protonation state. The best part is that you can use PDB2PQR web server and they will give you the corresponding CLI arguments for each option you ...


1

Welcome. The Protein-Ligand-complex is the complete protein with Ligand! If you only want to compare the two ligands, you can delete the rest of the proteins, or specify the input so only the ligand is choosen. (select Ligand and save selection. then use the function on that selections) But be aware that for Docking comparison you probably don't want to ...


1

Most universities have a ChemDraw site lincence, so you may want to check that for drawing a non–3D-embedded molecule. Alternatively there are many other programs. PyMOL is not really a good choice. Also there are online drawing tools everywhere, where you can download a SMILES (see below). Chemical formula is the wrong way to go, unless you are "...


1

Bizarrely, Obabel seems to have written a PDB that was incorrectly spaced for the OP as seen in Error pasing the following line in pdb If you can use python, rdkit is a great package for cheminformatics —best installed via conda though. It allows you do all sorts of things, such as match substructures, embed conformers, edit compounds, compute advanced ...


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Use OpenBabel. Something like babel -isdf file_in.sdf -opdb file_out.pdb.


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A PDB file has strict spacing rules as documented here. The coordinates should be: 31 - 38 Real(8.3) x Orthogonal coordinates for X. 39 - 46 Real(8.3) y Orthogonal coordinates for Y. 47 - 54 Real(8.3) z Orthogonal coordinates for Z. So trying this on your line: 'HETATM 1 C UNL 1 52355....


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You can visualize with Discovery Studio Visualizer and Schrodinger. Arpeggio and PLIP can generate output files of the different interactions.


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The answer is "Depends". But the best thing is always to look at what you ended up with and do some triaging before buying/synthesising anything. By triaging I mean filtering by its properties (.e.g. Lipinski, reactivity, synthetic feasibility etc. —discussed in this Bioinfo SE question). Score Regardless of docking software used, a forcefield free-...


1

I don't know that project's details, so cannot say officially, but undoubtedly it will be crystal structures of protein or models of point mutants based on structures of protein. Computer structure of the ligands based on force-field calculation Protein structures Firstly, HIV virus has been extensively studied by structural biologists, so most ...


1

The ultimate choice stems from your individual interests and not a scientific reason... but having said that some pointer of issues may be handy. I am assuming that you want to make an inhibitor that messes with the activity and not a ligand that binds somewhere and you then plan to add a moiety to make it a protac to get it degraded or to make it ...


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The smooth parameter is an optional keyword and command that changes the smoothing potential. If not provided, the default is 0.5 angstroms by default. Try passing 0 with this keyword in the AutoGrid Parameter File to turn off smoothing potential. See the AutoDock 4.2.5 documentation for more details.


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Let's get some definitions out of the way: RMSD, root mean square deviation, is a metric of distance of molecule A and molecule B. Think of it as average euclidean distance. It us casually called just 'deviation', but has nothing to do with standard deviation (the root of variance, 2nd moment). The units are Ångström. Reference RMSD is a term ...


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