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Positive Binding energy seen in docking studies
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Lwanda Babalo Madlanga
Positive Binding energy seen in docking studies
Do not forget to also perform a very rigorous analysis of the docking pose, cavity or pocket occupation (surface) and all the interactions, since sometimes these values imply that your ligand may not be coupling well in shape or electrostatically.
Do not forget to also perform a very rigorous analysis of the docking pose, cavity or pocket occupation (surface) and all the interactions, since sometimes these values imply that your ligand may not be coupling well in shape or electrostatically.
Jeffrey Godden makes a brilliant point about "zero binding energy". --- (Almost) everything makes sense only when viewed relatively. And that, which is absolute, cannot be divided into meaningful fragments for any comparison anyway. "Relative" also implies "subjectivity", because one has to pick some "fragments" of the whole for the comparison . . . In the case of protein-ligand binding (free) energy, what makes sense is comparing the interaction free energy of the ligand bound to the protein versus the free ligand in solution. What one wants to know, is the relative preference of the ligand for the two environments. The idea of "docking free energy function" is conceptually wrong. The protein-ligand docking "free" energy is definitely not "binding" energy, it is definitely not "free" energy, and I doubt we have the correct conceptual understanding of "energy" to be able to quantify it, i.e. if energy can actually be quantified at all . . .
Jeffrey Godden makes a brilliant point about "zero binding energy". --- (Almost) everything makes sense only when viewed relatively. And that, which is absolute, cannot be divided into meaningful fragments for any comparison anyway. "Relative" also implies "subjectivity", because one has to pick some "fragments" of the whole for the comparison . . . In the case of protein-ligand binding (free) energy, what makes sense is comparing the interaction free energy of the ligand bound to the protein versus the free ligand in solution. What one wants to know, is the relative preference of the ligand for the two environments. The idea of "docking free energy function" is conceptually wrong. The protein-ligand docking "free" energy is definitely not "binding" energy, it is definitely not "free" energy, and I doubt we have the correct conceptual understanding of "energy" to be able to quantify it, i.e. if energy can actually be quantified at all . . .
Re-install your program And when you work with one system Close autodock an reopen it to work with another system. Another suggestion maybe you are not selecting the best grid box or you didn't select center on the macromolecule option when choosing the grid
Re-install your program And when you work with one system Close autodock an reopen it to work with another system. Another suggestion maybe you are not selecting the best grid box or you didn't select center on the macromolecule option when choosing the grid
I have the same problem in my docking studies. I got positive binding energy by using autodock to study the interaction between specific ligand and protein. I also obtained positive binding energy when trying to dock the same ligand with different proteins. I do not know, what is the problem? Can anyone help me to find a solution for this problem? Thanks in advance.
I have the same problem in my docking studies. I got positive binding energy by using autodock to study the interaction between specific ligand and protein. I also obtained positive binding energy when trying to dock the same ligand with different proteins. I do not know, what is the problem? Can anyone help me to find a solution for this problem? Thanks in advance.
In my experience, energy values given by docking algorithms have little correlation with true binding affinities. At best, you can use these energies to rank the different resulting poses of a docking run with the same ligand and protein. Still, I would not trust these values even for ranking and I would visually inspect the all resulting poses to see if the putative binding pose proposed makes sense.
In my experience, energy values given by docking algorithms have little correlation with true binding affinities. At best, you can use these energies to rank the different resulting poses of a docking run with the same ligand and protein. Still, I would not trust these values even for ranking and I would visually inspect the all resulting poses to see if the putative binding pose proposed makes sense.
Did you used the Auto-Dock Vina up to now? Vina is considered to be the successor of AutoDock4.2 and comes with a new method-based, statistical scoring function that replaces the semi empirical force field of Auto-Dock. The advantages of Vina over AutoDock4.2 are its improved prediction accuracy and speed, which is not only due to the simplification of the scoring function, but also due to the capability of multi-threading in presence of multiple CPU cores. While the simplified scoring function still attempts to estimate free energies of binding in kcal/mol, the individual terms, such as hydrophobic contribution and hydrogen bonding are only provided as relative weights in the output. For any further information look at to the address of its as follows Website: http://vina.scripps.edu
Did you used the Auto-Dock Vina up to now? Vina is considered to be the successor of AutoDock4.2 and comes with a new method-based, statistical scoring function that replaces the semi empirical force field of Auto-Dock. The advantages of Vina over AutoDock4.2 are its improved prediction accuracy and speed, which is not only due to the simplification of the scoring function, but also due to the capability of multi-threading in presence of multiple CPU cores. While the simplified scoring function still attempts to estimate free energies of binding in kcal/mol, the individual terms, such as hydrophobic contribution and hydrogen bonding are only provided as relative weights in the output. For any further information look at to the address of its as follows Website: http://vina.scripps.edu
Just to underscore Antonio de la Vega de Leon's excellent characterization of the situation i'd add: What do you think a binding energy of zero, returned from any docking software, would mean? It would be nice if it meant there was no interaction at all, but could that ever really occur in the real world? So if zero binding energy had no likely correspondence in reality, I'd assert that negative or positive energies are just markings on some arbitrary scale (like on an electric guitar amplifier). However, we will remain hopeful that they often have relative meaning.
Just to underscore Antonio de la Vega de Leon's excellent characterization of the situation i'd add: What do you think a binding energy of zero, returned from any docking software, would mean? It would be nice if it meant there was no interaction at all, but could that ever really occur in the real world? So if zero binding energy had no likely correspondence in reality, I'd assert that negative or positive energies are just markings on some arbitrary scale (like on an electric guitar amplifier). However, we will remain hopeful that they often have relative meaning.
In my experience, energy values given by docking algorithms have little correlation with true binding affinities. At best, you can use these energies to rank the different resulting poses of a docking run with the same ligand and protein. Still, I would not trust these values even for ranking and I would visually inspect the all resulting poses to see if the putative binding pose proposed makes sense.
In my experience, energy values given by docking algorithms have little correlation with true binding affinities. At best, you can use these energies to rank the different resulting poses of a docking run with the same ligand and protein. Still, I would not trust these values even for ranking and I would visually inspect the all resulting poses to see if the putative binding pose proposed makes sense.
Do not forget to also perform a very rigorous analysis of the docking pose, cavity or pocket occupation (surface) and all the interactions, since sometimes these values imply that your ligand may not be coupling well in shape or electrostatically.
Do not forget to also perform a very rigorous analysis of the docking pose, cavity or pocket occupation (surface) and all the interactions, since sometimes these values imply that your ligand may not be coupling well in shape or electrostatically.
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Jeffrey Godden makes a brilliant point about "zero binding energy".
---
(Almost) everything makes sense only when viewed relatively. And that, which is absolute, cannot be divided into meaningful fragments for any comparison anyway. "Relative" also implies "subjectivity", because one has to pick some "fragments" of the whole for the comparison . . .
In the case of protein-ligand binding (free) energy, what makes sense is comparing the interaction free energy of the ligand bound to the protein versus the free ligand in solution. What one wants to know, is the relative preference of the ligand for the two environments. The idea of "docking free energy function" is conceptually wrong.
The protein-ligand docking "free" energy is definitely not "binding" energy, it is definitely not "free" energy, and I doubt we have the correct conceptual understanding of "energy" to be able to quantify it, i.e. if energy can actually be quantified at all . . .
Jeffrey Godden makes a brilliant point about "zero binding energy".
---
(Almost) everything makes sense only when viewed relatively. And that, which is absolute, cannot be divided into meaningful fragments for any comparison anyway. "Relative" also implies "subjectivity", because one has to pick some "fragments" of the whole for the comparison . . .
In the case of protein-ligand binding (free) energy, what makes sense is comparing the interaction free energy of the ligand bound to the protein versus the free ligand in solution. What one wants to know, is the relative preference of the ligand for the two environments. The idea of "docking free energy function" is conceptually wrong.
The protein-ligand docking "free" energy is definitely not "binding" energy, it is definitely not "free" energy, and I doubt we have the correct conceptual understanding of "energy" to be able to quantify it, i.e. if energy can actually be quantified at all . . .
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VOTE
Re-install your program
And when you work with one system
Close autodock an reopen it to work with another system.
Another suggestion maybe you are not selecting the best grid box or you didn't select center on the macromolecule option when choosing the grid
Re-install your program
And when you work with one system
Close autodock an reopen it to work with another system.
Another suggestion maybe you are not selecting the best grid box or you didn't select center on the macromolecule option when choosing the grid
More
VOTE
It mean that affinity is so low. The affinity is related with free energy of Gibbs that to probe docking affinity must be negative.
It mean that affinity is so low. The affinity is related with free energy of Gibbs that to probe docking affinity must be negative.
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Do you need Auto-Dock Vina for installing ?
Do you need Auto-Dock Vina for installing ?
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I have the same problem in my docking studies. I got positive binding energy by using autodock to study the interaction between specific ligand and protein. I also obtained positive binding energy when trying to dock the same ligand with different proteins. I do not know, what is the problem?
Can anyone help me to find a solution for this problem?
Thanks in advance.
I have the same problem in my docking studies. I got positive binding energy by using autodock to study the interaction between specific ligand and protein. I also obtained positive binding energy when trying to dock the same ligand with different proteins. I do not know, what is the problem?
Can anyone help me to find a solution for this problem?
Thanks in advance.
More
VOTE
In my experience, energy values given by docking algorithms have little correlation with true binding affinities. At best, you can use these energies to rank the different resulting poses of a docking run with the same ligand and protein. Still, I would not trust these values even for ranking and I would visually inspect the all resulting poses to see if the putative binding pose proposed makes sense.
In my experience, energy values given by docking algorithms have little correlation with true binding affinities. At best, you can use these energies to rank the different resulting poses of a docking run with the same ligand and protein. Still, I would not trust these values even for ranking and I would visually inspect the all resulting poses to see if the putative binding pose proposed makes sense.
More
VOTE
Did you used the Auto-Dock Vina up to now?
Vina is considered to be the successor of AutoDock4.2 and comes with a new method-based, statistical scoring function that replaces the semi empirical force field of Auto-Dock.
The advantages of Vina over AutoDock4.2 are its improved prediction accuracy and speed, which is not only due to the simplification of the scoring function, but also due to the capability of multi-threading in presence of multiple CPU cores.
While the simplified scoring function still attempts to estimate free energies of binding in kcal/mol, the individual terms, such as hydrophobic contribution and hydrogen bonding are only provided as relative weights in the output.
For any further information look at to the address of its as follows
Website: http://vina.scripps.edu
Did you used the Auto-Dock Vina up to now?
Vina is considered to be the successor of AutoDock4.2 and comes with a new method-based, statistical scoring function that replaces the semi empirical force field of Auto-Dock.
The advantages of Vina over AutoDock4.2 are its improved prediction accuracy and speed, which is not only due to the simplification of the scoring function, but also due to the capability of multi-threading in presence of multiple CPU cores.
While the simplified scoring function still attempts to estimate free energies of binding in kcal/mol, the individual terms, such as hydrophobic contribution and hydrogen bonding are only provided as relative weights in the output.
For any further information look at to the address of its as follows
Website: http://vina.scripps.edu
More
VOTE
Just to underscore Antonio de la Vega de Leon's excellent characterization of the situation i'd add: What do you think a binding energy of zero, returned from any docking software, would mean? It would be nice if it meant there was no interaction at all, but could that ever really occur in the real world? So if zero binding energy had no likely correspondence in reality, I'd assert that negative or positive energies are just markings on some arbitrary scale (like on an electric guitar amplifier). However, we will remain hopeful that they often have relative meaning.
Just to underscore Antonio de la Vega de Leon's excellent characterization of the situation i'd add: What do you think a binding energy of zero, returned from any docking software, would mean? It would be nice if it meant there was no interaction at all, but could that ever really occur in the real world? So if zero binding energy had no likely correspondence in reality, I'd assert that negative or positive energies are just markings on some arbitrary scale (like on an electric guitar amplifier). However, we will remain hopeful that they often have relative meaning.
More
VOTE
Thank you Antonio Del la Vega De Leon, Majid Monajjemi and Jeffrey Godden. Your answers really helped me understand.
Thank you Antonio Del la Vega De Leon, Majid Monajjemi and Jeffrey Godden. Your answers really helped me understand.
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VOTE
In my experience, energy values given by docking algorithms have little correlation with true binding affinities. At best, you can use these energies to rank the different resulting poses of a docking run with the same ligand and protein. Still, I would not trust these values even for ranking and I would visually inspect the all resulting poses to see if the putative binding pose proposed makes sense.
In my experience, energy values given by docking algorithms have little correlation with true binding affinities. At best, you can use these energies to rank the different resulting poses of a docking run with the same ligand and protein. Still, I would not trust these values even for ranking and I would visually inspect the all resulting poses to see if the putative binding pose proposed makes sense.
More
VOTE