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Xinheng-He / ti_toturial

A toturial for TI in Amber
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AMBER caculates TI and FEP #2

Open Philjphuang opened 5 months ago

Philjphuang commented 5 months ago

When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?

Xinheng-He commented 5 months ago

Maybe you can run longer simulations.

Original

From:"Philjphuang"< @.*** >;

Date:2024/4/1 14:08

To:"Xinheng-He/ti_toturial"< @.*** >;

CC:"Subscribed"< @.*** >;

Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?

— Reply to this email directly, view it on GitHub, or unsubscribe. You are receiving this because you are subscribed to this thread.Message ID: @.***>

Philjphuang commented 5 months ago

Thank you.Your toturial is very useful. 

Juping Huang @.***

---Original--- From: @.> Date: Mon, Apr 1, 2024 20:07 PM To: @.>; Cc: @.**@.>; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Maybe you can run longer simulations.

Original

From:"Philjphuang"< @.*** &gt;;

Date:2024/4/1 14:08

To:"Xinheng-He/ti_toturial"< @.*** &gt;;

CC:"Subscribed"< @.*** &gt;;

Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?

— Reply to this email directly, view it on GitHub, or unsubscribe. You are receiving this because you are subscribed to this thread.Message ID: @.&gt; — Reply to this email directly, view it on GitHub, or unsubscribe. You are receiving this because you authored the thread.Message ID: @.>

Philjphuang commented 5 months ago

Hi, when I used AMBER to calculate TI, the Ti result was normal and the FEP result was abnormal. In the FEP result, the ddG for complex is close to twice the ddG for apoprotein, and this is also true across lambda.

Juping Huang @.***

---Original--- From: @.> Date: Mon, Apr 1, 2024 20:07 PM To: @.>; Cc: @.**@.>; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Maybe you can run longer simulations.

Original

From:"Philjphuang"< @.*** &gt;;

Date:2024/4/1 14:08

To:"Xinheng-He/ti_toturial"< @.*** &gt;;

CC:"Subscribed"< @.*** &gt;;

Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?

— Reply to this email directly, view it on GitHub, or unsubscribe. You are receiving this because you are subscribed to this thread.Message ID: @.&gt; — Reply to this email directly, view it on GitHub, or unsubscribe. You are receiving this because you authored the thread.Message ID: @.>

Xinheng-He commented 5 months ago

I think it's normal to produce different result according to different algorithms. BTW, how you use Amber to calculate FEP?

Original

From:"Philjphuang"< @.*** >;

Date:2024/4/3 10:19

To:"Xinheng-He/ti_toturial"< @.*** >;

CC:"Xinheng-He"< @. >;"Comment"< @. >;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Hi, when I used AMBER to calculate TI, the Ti result was normal and the FEP result was abnormal. In the FEP result, the ddG for complex is close to twice the ddG for apoprotein, and this is also true across lambda.

Juping&nbsp;Huang @.***

---Original--- From: @.&gt; Date: Mon, Apr 1, 2024 20:07 PM To: @.&gt;; Cc: @.**@.&gt;; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Maybe you can run longer simulations.

Original

From:"Philjphuang"< @.*** &amp;gt;;

Date:2024/4/1 14:08

To:"Xinheng-He/ti_toturial"< @.*** &amp;gt;;

CC:"Subscribed"< @.*** &amp;gt;;

Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?

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Philjphuang commented 5 months ago

Basically follow your tutorial, but I calculated the ddG after antibody mutation, mutated the amino acid of the antibody using rosetta, and then performed Timerge, simulated under different lambdas. For example, the ddG of TI is -0.9, and the ddG of FEP is -136, which is particularly different. In FEP, the ddG of the  complex is always close to twice the ddG of the antibody, so the final ddG of the FEP is abnormal.The ligand in your tutorial is a small molecule, and my ligand is an antibody, is it possible that this caused the error?

Juping Huang @.***

---Original--- From: @.> Date: Wed, Apr 3, 2024 10:21 AM To: @.>; Cc: @.**@.>; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think it's normal to produce different result according to different algorithms. BTW, how you use Amber to calculate FEP?

Original

From:"Philjphuang"< @.*** &gt;;

Date:2024/4/3 10:19

To:"Xinheng-He/ti_toturial"< @.*** &gt;;

CC:"Xinheng-He"< @. &gt;;"Comment"< @. &gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Hi, when I used AMBER to calculate TI, the Ti result was normal and the FEP result was abnormal. In the FEP result, the ddG for complex is close to twice the ddG for apoprotein, and this is also true across lambda.

Juping&amp;nbsp;Huang
@.***

---Original---
From: @.&amp;gt;
Date: Mon, Apr 1, 2024 20:07 PM
To: @.&amp;gt;;
Cc: @.**@.&amp;gt;;
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Maybe you can run longer simulations.

Original

From:"Philjphuang"< @.*** &amp;amp;gt;;

Date:2024/4/1 14:08

To:"Xinheng-He/ti_toturial"< @.*** &amp;amp;gt;;

CC:"Subscribed"< @.*** &amp;amp;gt;;

Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?

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Xinheng-He commented 5 months ago

I think I also have toturial for proteins. The mutation of residue is different from ligand.

Original

From:"Philjphuang"< @.*** >;

Date:2024/4/3 11:52

To:"Xinheng-He/ti_toturial"< @.*** >;

CC:"Xinheng-He"< @. >;"Comment"< @. >;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Basically follow your tutorial, but I calculated the ddG after antibody mutation, mutated the amino acid of the antibody using rosetta, and then performed Timerge, simulated under different lambdas. For example, the ddG of TI is -0.9, and the ddG of FEP is -136, which is particularly different. In FEP, the ddG of the&nbsp; complex is always close to twice the ddG of the antibody, so the final ddG of the FEP is abnormal.The ligand in your tutorial is a small molecule, and my ligand is an antibody, is it possible that this caused the error?

Juping&nbsp;Huang @.***

---Original--- From: @.&gt; Date: Wed, Apr 3, 2024 10:21 AM To: @.&gt;; Cc: @.**@.&gt;; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think it's normal to produce different result according to different algorithms. BTW, how you use Amber to calculate FEP?

Original

From:"Philjphuang"< @.*** &amp;gt;;

Date:2024/4/3 10:19

To:"Xinheng-He/ti_toturial"< @.*** &amp;gt;;

CC:"Xinheng-He"< @. &amp;gt;;"Comment"< @. &amp;gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Hi, when I used AMBER to calculate TI, the Ti result was normal and the FEP result was abnormal. In the FEP result, the ddG for complex is close to twice the ddG for apoprotein, and this is also true across lambda.

Juping&amp;amp;nbsp;Huang
@.***

---Original---
From: @.&amp;amp;gt;
Date: Mon, Apr 1, 2024 20:07 PM
To: @.&amp;amp;gt;;
Cc: @.**@.&amp;amp;gt;;
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2) 

Maybe you can run longer simulations.    

Original    

From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;gt;;    

Date:2024/4/1 14:08    

To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;gt;;    

CC:"Subscribed"< ***@***.*** &amp;amp;amp;amp;gt;;    

Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)    

When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?    

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Reply to this email directly, view it on GitHub, or unsubscribe.    
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Philjphuang commented 5 months ago

I'm learning about your protein mutation. The difference is that you extract the water box and the counterions of the complex, and the complex and the protein use the same water box and counterions. I used the water box and counterion generated by tleap for the protein and complex respectively. Is it possible that the difference in the size of the water box and counterion caused the abnormal FEP results, but the normal TI results?

Juping Huang @.***

---Original--- From: @.> Date: Wed, Apr 3, 2024 11:54 AM To: @.>; Cc: @.**@.>; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think I also have toturial for proteins. The mutation of residue is different from ligand.

Original

From:"Philjphuang"< @.*** &gt;;

Date:2024/4/3 11:52

To:"Xinheng-He/ti_toturial"< @.*** &gt;;

CC:"Xinheng-He"< @. &gt;;"Comment"< @. &gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Basically follow your tutorial, but I calculated the ddG after antibody mutation, mutated the amino acid of the antibody using rosetta, and then performed Timerge, simulated under different lambdas. For example, the ddG of TI is -0.9, and the ddG of FEP is -136, which is particularly different. In FEP, the ddG of the&amp;nbsp; complex is always close to twice the ddG of the antibody, so the final ddG of the FEP is abnormal.The ligand in your tutorial is a small molecule, and my ligand is an antibody, is it possible that this caused the error?

Juping&amp;nbsp;Huang
@.***

---Original---
From: @.&amp;gt;
Date: Wed, Apr 3, 2024 10:21 AM
To: @.&amp;gt;;
Cc: @.**@.&amp;gt;;
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think it's normal to produce different result according to different algorithms. BTW, how you use Amber to calculate FEP?

Original

From:"Philjphuang"< @.*** &amp;amp;gt;;

Date:2024/4/3 10:19

To:"Xinheng-He/ti_toturial"< @.*** &amp;amp;gt;;

CC:"Xinheng-He"< @. &amp;amp;gt;;"Comment"< @. &amp;amp;gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2) 

Hi, when I used AMBER to calculate TI, the Ti result was normal and the FEP result was abnormal. In the FEP result, the ddG for complex is close to twice the ddG for apoprotein, and this is also true across lambda.    

Juping&amp;amp;amp;amp;nbsp;Huang    
***@***.***    

---Original---    
From: ***@***.***&amp;amp;amp;amp;gt;    
Date: Mon, Apr 1, 2024 20:07 PM    
To: ***@***.***&amp;amp;amp;amp;gt;;    
Cc: ***@***.******@***.***&amp;amp;amp;amp;gt;;    
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)    

 Maybe you can run longer simulations.     

 Original     

 From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 Date:2024/4/1 14:08     

 To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 CC:"Subscribed"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)     

 When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?     

 —     
 Reply to this email directly, view it on GitHub, or unsubscribe.     
 You are receiving this because you are subscribed to this thread.Message ID: ***@***.***&amp;amp;amp;amp;amp;gt;     
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Xinheng-He commented 5 months ago

I think it's possible.

Original

From:"Philjphuang"< @.*** >;

Date:2024/4/3 12:08

To:"Xinheng-He/ti_toturial"< @.*** >;

CC:"Xinheng-He"< @. >;"Comment"< @. >;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I'm learning about your protein mutation. The difference is that you extract the water box and the counterions of the complex, and the complex and the protein use the same water box and counterions. I used the water box and counterion generated by tleap for the protein and complex respectively. Is it possible that the difference in the size of the water box and counterion caused the abnormal FEP results, but the normal TI results?

Juping&nbsp;Huang @.***

---Original--- From: @.&gt; Date: Wed, Apr 3, 2024 11:54 AM To: @.&gt;; Cc: @.**@.&gt;; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think I also have toturial for proteins. The mutation of residue is different from ligand.

Original

From:"Philjphuang"< @.*** &amp;gt;;

Date:2024/4/3 11:52

To:"Xinheng-He/ti_toturial"< @.*** &amp;gt;;

CC:"Xinheng-He"< @. &amp;gt;;"Comment"< @. &amp;gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Basically follow your tutorial, but I calculated the ddG after antibody mutation, mutated the amino acid of the antibody using rosetta, and then performed Timerge, simulated under different lambdas. For example, the ddG of TI is -0.9, and the ddG of FEP is -136, which is particularly different. In FEP, the ddG of the&amp;amp;nbsp; complex is always close to twice the ddG of the antibody, so the final ddG of the FEP is abnormal.The ligand in your tutorial is a small molecule, and my ligand is an antibody, is it possible that this caused the error?

Juping&amp;amp;nbsp;Huang
@.***

---Original---
From: @.&amp;amp;gt;
Date: Wed, Apr 3, 2024 10:21 AM
To: @.&amp;amp;gt;;
Cc: @.**@.&amp;amp;gt;;
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2) 

I think it's normal to produce different result according to different algorithms. BTW, how you use Amber to calculate FEP?    

Original    

From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;gt;;    

Date:2024/4/3 10:19    

To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;gt;;    

CC:"Xinheng-He"< ***@***.*** &amp;amp;amp;amp;gt;;"Comment"< ***@***.*** &amp;amp;amp;amp;gt;;    

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)    

 Hi, when I used AMBER to calculate TI, the Ti result was normal and the FEP result was abnormal. In the FEP result, the ddG for complex is close to twice the ddG for apoprotein, and this is also true across lambda.     

 Juping&amp;amp;amp;amp;amp;nbsp;Huang     
 ***@***.***     

 ---Original---     
 From: ***@***.***&amp;amp;amp;amp;amp;gt;     
 Date: Mon, Apr 1, 2024 20:07 PM     
 To: ***@***.***&amp;amp;amp;amp;amp;gt;;     
 Cc: ***@***.******@***.***&amp;amp;amp;amp;amp;gt;;     
 Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)     

  Maybe you can run longer simulations.      

  Original      

  From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;amp;gt;;      

  Date:2024/4/1 14:08      

  To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;amp;gt;;      

  CC:"Subscribed"< ***@***.*** &amp;amp;amp;amp;amp;amp;gt;;      

  Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)      

  When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?      

  —      
  Reply to this email directly, view it on GitHub, or unsubscribe.      
  You are receiving this because you are subscribed to this thread.Message ID: ***@***.***&amp;amp;amp;amp;amp;amp;gt;      
 —     
 Reply to this email directly, view it on GitHub, or unsubscribe.     
 You are receiving this because you authored the thread.Message ID: ***@***.***&amp;amp;amp;amp;amp;gt;     
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Philjphuang commented 5 months ago

Thank you very much.

Juping Huang @.***

---Original--- From: @.> Date: Wed, Apr 3, 2024 16:35 PM To: @.>; Cc: @.**@.>; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think it's possible.

Original

From:"Philjphuang"< @.*** &gt;;

Date:2024/4/3 12:08

To:"Xinheng-He/ti_toturial"< @.*** &gt;;

CC:"Xinheng-He"< @. &gt;;"Comment"< @. &gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I'm learning about your protein mutation. The difference is that you extract the water box and the counterions of the complex, and the complex and the protein use the same water box and counterions. I used the water box and counterion generated by tleap for the protein and complex respectively. Is it possible that the difference in the size of the water box and counterion caused the abnormal FEP results, but the normal TI results?

Juping&amp;nbsp;Huang
@.***

---Original---
From: @.&amp;gt;
Date: Wed, Apr 3, 2024 11:54 AM
To: @.&amp;gt;;
Cc: @.**@.&amp;gt;;
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think I also have toturial for proteins. The mutation of residue is different from ligand.

Original

From:"Philjphuang"< @.*** &amp;amp;gt;;

Date:2024/4/3 11:52

To:"Xinheng-He/ti_toturial"< @.*** &amp;amp;gt;;

CC:"Xinheng-He"< @. &amp;amp;gt;;"Comment"< @. &amp;amp;gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2) 

Basically follow your tutorial, but I calculated the ddG after antibody mutation, mutated the amino acid of the antibody using rosetta, and then performed Timerge, simulated under different lambdas. For example, the ddG of TI is -0.9, and the ddG of FEP is -136, which is particularly different. In FEP, the ddG of the&amp;amp;amp;amp;nbsp; complex is always close to twice the ddG of the antibody, so the final ddG of the FEP is abnormal.The ligand in your tutorial is a small molecule, and my ligand is an antibody, is it possible that this caused the error?    

Juping&amp;amp;amp;amp;nbsp;Huang    
***@***.***    

---Original---    
From: ***@***.***&amp;amp;amp;amp;gt;    
Date: Wed, Apr 3, 2024 10:21 AM    
To: ***@***.***&amp;amp;amp;amp;gt;;    
Cc: ***@***.******@***.***&amp;amp;amp;amp;gt;;    
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)    

 I think it's normal to produce different result according to different algorithms. BTW, how you use Amber to calculate FEP?     

 Original     

 From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 Date:2024/4/3 10:19     

 To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 CC:"Xinheng-He"< ***@***.*** &amp;amp;amp;amp;amp;gt;;"Comment"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)     

  Hi, when I used AMBER to calculate TI, the Ti result was normal and the FEP result was abnormal. In the FEP result, the ddG for complex is close to twice the ddG for apoprotein, and this is also true across lambda.      

  Juping&amp;amp;amp;amp;amp;amp;nbsp;Huang      
  ***@***.***      

  ---Original---      
  From: ***@***.***&amp;amp;amp;amp;amp;amp;gt;      
  Date: Mon, Apr 1, 2024 20:07 PM      
  To: ***@***.***&amp;amp;amp;amp;amp;amp;gt;;      
  Cc: ***@***.******@***.***&amp;amp;amp;amp;amp;amp;gt;;      
  Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)      

   Maybe you can run longer simulations.       

   Original       

   From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;gt;;       

   Date:2024/4/1 14:08       

   To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;gt;;       

   CC:"Subscribed"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;gt;;       

   Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)       

   When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?       

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   Reply to this email directly, view it on GitHub, or unsubscribe.       
   You are receiving this because you are subscribed to this thread.Message ID: ***@***.***&amp;amp;amp;amp;amp;amp;amp;gt;       
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Philjphuang commented 5 months ago

Hello. Have you done antibody and receptor protein systems? After  amino acid mutation, DDG was calculated using FEP.

Juping Huang @.***

---Original--- From: @.> Date: Wed, Apr 3, 2024 16:35 PM To: @.>; Cc: @.**@.>; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think it's possible.

Original

From:"Philjphuang"< @.*** &gt;;

Date:2024/4/3 12:08

To:"Xinheng-He/ti_toturial"< @.*** &gt;;

CC:"Xinheng-He"< @. &gt;;"Comment"< @. &gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I'm learning about your protein mutation. The difference is that you extract the water box and the counterions of the complex, and the complex and the protein use the same water box and counterions. I used the water box and counterion generated by tleap for the protein and complex respectively. Is it possible that the difference in the size of the water box and counterion caused the abnormal FEP results, but the normal TI results?

Juping&amp;nbsp;Huang
@.***

---Original---
From: @.&amp;gt;
Date: Wed, Apr 3, 2024 11:54 AM
To: @.&amp;gt;;
Cc: @.**@.&amp;gt;;
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think I also have toturial for proteins. The mutation of residue is different from ligand.

Original

From:"Philjphuang"< @.*** &amp;amp;gt;;

Date:2024/4/3 11:52

To:"Xinheng-He/ti_toturial"< @.*** &amp;amp;gt;;

CC:"Xinheng-He"< @. &amp;amp;gt;;"Comment"< @. &amp;amp;gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2) 

Basically follow your tutorial, but I calculated the ddG after antibody mutation, mutated the amino acid of the antibody using rosetta, and then performed Timerge, simulated under different lambdas. For example, the ddG of TI is -0.9, and the ddG of FEP is -136, which is particularly different. In FEP, the ddG of the&amp;amp;amp;amp;nbsp; complex is always close to twice the ddG of the antibody, so the final ddG of the FEP is abnormal.The ligand in your tutorial is a small molecule, and my ligand is an antibody, is it possible that this caused the error?    

Juping&amp;amp;amp;amp;nbsp;Huang    
***@***.***    

---Original---    
From: ***@***.***&amp;amp;amp;amp;gt;    
Date: Wed, Apr 3, 2024 10:21 AM    
To: ***@***.***&amp;amp;amp;amp;gt;;    
Cc: ***@***.******@***.***&amp;amp;amp;amp;gt;;    
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)    

 I think it's normal to produce different result according to different algorithms. BTW, how you use Amber to calculate FEP?     

 Original     

 From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 Date:2024/4/3 10:19     

 To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 CC:"Xinheng-He"< ***@***.*** &amp;amp;amp;amp;amp;gt;;"Comment"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)     

  Hi, when I used AMBER to calculate TI, the Ti result was normal and the FEP result was abnormal. In the FEP result, the ddG for complex is close to twice the ddG for apoprotein, and this is also true across lambda.      

  Juping&amp;amp;amp;amp;amp;amp;nbsp;Huang      
  ***@***.***      

  ---Original---      
  From: ***@***.***&amp;amp;amp;amp;amp;amp;gt;      
  Date: Mon, Apr 1, 2024 20:07 PM      
  To: ***@***.***&amp;amp;amp;amp;amp;amp;gt;;      
  Cc: ***@***.******@***.***&amp;amp;amp;amp;amp;amp;gt;;      
  Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)      

   Maybe you can run longer simulations.       

   Original       

   From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;gt;;       

   Date:2024/4/1 14:08       

   To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;gt;;       

   CC:"Subscribed"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;gt;;       

   Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)       

   When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?       

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Xinheng-He commented 5 months ago

Not yet.

---Original--- From: @.> Date: Thu, Apr 4, 2024 11:26 AM To: @.>; Cc: @.**@.>; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Hello. Have you done antibody and receptor protein systems? After&nbsp; amino acid mutation, DDG was calculated using FEP.

Juping&nbsp;Huang @.***

---Original--- From: @.&gt; Date: Wed, Apr 3, 2024 16:35 PM To: @.&gt;; Cc: @.**@.&gt;; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think it's possible.

Original

From:"Philjphuang"< @.*** &amp;gt;;

Date:2024/4/3 12:08

To:"Xinheng-He/ti_toturial"< @.*** &amp;gt;;

CC:"Xinheng-He"< @. &amp;gt;;"Comment"< @. &amp;gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I'm learning about your protein mutation. The difference is that you extract the water box and the counterions of the complex, and the complex and the protein use the same water box and counterions. I used the water box and counterion generated by tleap for the protein and complex respectively. Is it possible that the difference in the size of the water box and counterion caused the abnormal FEP results, but the normal TI results?

Juping&amp;amp;nbsp;Huang
@.***

---Original---
From: @.&amp;amp;gt;
Date: Wed, Apr 3, 2024 11:54 AM
To: @.&amp;amp;gt;;
Cc: @.**@.&amp;amp;gt;;
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2) 

I think I also have toturial for proteins. The mutation of residue is different from ligand.    

Original    

From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;gt;;    

Date:2024/4/3 11:52    

To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;gt;;    

CC:"Xinheng-He"< ***@***.*** &amp;amp;amp;amp;gt;;"Comment"< ***@***.*** &amp;amp;amp;amp;gt;;    

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)    

 Basically follow your tutorial, but I calculated the ddG after antibody mutation, mutated the amino acid of the antibody using rosetta, and then performed Timerge, simulated under different lambdas. For example, the ddG of TI is -0.9, and the ddG of FEP is -136, which is particularly different. In FEP, the ddG of the&amp;amp;amp;amp;amp;nbsp; complex is always close to twice the ddG of the antibody, so the final ddG of the FEP is abnormal.The ligand in your tutorial is a small molecule, and my ligand is an antibody, is it possible that this caused the error?     

 Juping&amp;amp;amp;amp;amp;nbsp;Huang     
 ***@***.***     

 ---Original---     
 From: ***@***.***&amp;amp;amp;amp;amp;gt;     
 Date: Wed, Apr 3, 2024 10:21 AM     
 To: ***@***.***&amp;amp;amp;amp;amp;gt;;     
 Cc: ***@***.******@***.***&amp;amp;amp;amp;amp;gt;;     
 Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)     

  I think it's normal to produce different result according to different algorithms. BTW, how you use Amber to calculate FEP?      

  Original      

  From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;amp;gt;;      

  Date:2024/4/3 10:19      

  To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;amp;gt;;      

  CC:"Xinheng-He"< ***@***.*** &amp;amp;amp;amp;amp;amp;gt;;"Comment"< ***@***.*** &amp;amp;amp;amp;amp;amp;gt;;      

  Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)      

   Hi, when I used AMBER to calculate TI, the Ti result was normal and the FEP result was abnormal. In the FEP result, the ddG for complex is close to twice the ddG for apoprotein, and this is also true across lambda.       

   Juping&amp;amp;amp;amp;amp;amp;amp;nbsp;Huang       
   ***@***.***       

   ---Original---       
   From: ***@***.***&amp;amp;amp;amp;amp;amp;amp;gt;       
   Date: Mon, Apr 1, 2024 20:07 PM       
   To: ***@***.***&amp;amp;amp;amp;amp;amp;amp;gt;;       
   Cc: ***@***.******@***.***&amp;amp;amp;amp;amp;amp;amp;gt;;       
   Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)       

    Maybe you can run longer simulations.        

    Original        

    From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;amp;gt;;        

    Date:2024/4/1 14:08        

    To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;amp;gt;;        

    CC:"Subscribed"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;amp;gt;;        

    Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)        

    When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?        

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Philjphuang commented 5 months ago

Ok. Thank you 

Juping Huang @.***

---Original--- From: @.> Date: Thu, Apr 4, 2024 11:32 AM To: @.>; Cc: @.**@.>; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Not yet.

---Original--- From: @.&gt; Date: Thu, Apr 4, 2024 11:26 AM To: @.&gt;; Cc: @.**@.&gt;; Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

Hello.
Have you done antibody and receptor protein systems? After&amp;nbsp; amino acid mutation, DDG was calculated using FEP.

Juping&amp;nbsp;Huang
@.***

---Original---
From: @.&amp;gt;
Date: Wed, Apr 3, 2024 16:35 PM
To: @.&amp;gt;;
Cc: @.**@.&amp;gt;;
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)

I think it's possible.

Original

From:"Philjphuang"< @.*** &amp;amp;gt;;

Date:2024/4/3 12:08

To:"Xinheng-He/ti_toturial"< @.*** &amp;amp;gt;;

CC:"Xinheng-He"< @. &amp;amp;gt;;"Comment"< @. &amp;amp;gt;;

Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2) 

I'm learning about your protein mutation. The difference is that you extract the water box and the counterions of the complex, and the complex and the protein use the same water box and counterions. I used the water box and counterion generated by tleap for the protein and complex respectively. Is it possible that the difference in the size of the water box and counterion caused the abnormal FEP results, but the normal TI results?    

Juping&amp;amp;amp;amp;nbsp;Huang    
***@***.***    

---Original---    
From: ***@***.***&amp;amp;amp;amp;gt;    
Date: Wed, Apr 3, 2024 11:54 AM    
To: ***@***.***&amp;amp;amp;amp;gt;;    
Cc: ***@***.******@***.***&amp;amp;amp;amp;gt;;    
Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)    

 I think I also have toturial for proteins. The mutation of residue is different from ligand.     

 Original     

 From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 Date:2024/4/3 11:52     

 To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 CC:"Xinheng-He"< ***@***.*** &amp;amp;amp;amp;amp;gt;;"Comment"< ***@***.*** &amp;amp;amp;amp;amp;gt;;     

 Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)     

  Basically follow your tutorial, but I calculated the ddG after antibody mutation, mutated the amino acid of the antibody using rosetta, and then performed Timerge, simulated under different lambdas. For example, the ddG of TI is -0.9, and the ddG of FEP is -136, which is particularly different. In FEP, the ddG of the&amp;amp;amp;amp;amp;amp;nbsp; complex is always close to twice the ddG of the antibody, so the final ddG of the FEP is abnormal.The ligand in your tutorial is a small molecule, and my ligand is an antibody, is it possible that this caused the error?      

  Juping&amp;amp;amp;amp;amp;amp;nbsp;Huang      
  ***@***.***      

  ---Original---      
  From: ***@***.***&amp;amp;amp;amp;amp;amp;gt;      
  Date: Wed, Apr 3, 2024 10:21 AM      
  To: ***@***.***&amp;amp;amp;amp;amp;amp;gt;;      
  Cc: ***@***.******@***.***&amp;amp;amp;amp;amp;amp;gt;;      
  Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)      

   I think it's normal to produce different result according to different algorithms. BTW, how you use Amber to calculate FEP?       

   Original       

   From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;gt;;       

   Date:2024/4/3 10:19       

   To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;gt;;       

   CC:"Xinheng-He"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;gt;;"Comment"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;gt;;       

   Subject:Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)       

    Hi, when I used AMBER to calculate TI, the Ti result was normal and the FEP result was abnormal. In the FEP result, the ddG for complex is close to twice the ddG for apoprotein, and this is also true across lambda.        

    Juping&amp;amp;amp;amp;amp;amp;amp;amp;nbsp;Huang        
    ***@***.***        

    ---Original---        
    From: ***@***.***&amp;amp;amp;amp;amp;amp;amp;amp;gt;        
    Date: Mon, Apr 1, 2024 20:07 PM        
    To: ***@***.***&amp;amp;amp;amp;amp;amp;amp;amp;gt;;        
    Cc: ***@***.******@***.***&amp;amp;amp;amp;amp;amp;amp;amp;gt;;        
    Subject: Re: [Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)        

     Maybe you can run longer simulations.         

     Original         

     From:"Philjphuang"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;;         

     Date:2024/4/1 14:08         

     To:"Xinheng-He/ti_toturial"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;;         

     CC:"Subscribed"< ***@***.*** &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;;         

     Subject:[Xinheng-He/ti_toturial] AMBER caculates TI and FEP (Issue #2)         

     When calculating the binding free energy change caused by mutation of protein amino acids using AMBER's TI for FEP, when calculating the complex, the energy calculated in a certain window is negative infinity. How to solve this issue?         

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