[gmx-users] protein-ligand umbrella sampling

abhisek Mondal abhisek.mndl at gmail.com
Wed Nov 23 07:28:52 CET 2016


Hi,

I have came across that there are many ways of pulling, although have no
idea which is to apply and when. A descriptive tutorial is what I'm missing.

However, I'm thinking to go for distance pulling in all dimension as also
suggested here
<http://thread.gmane.org/gmane.science.biology.gromacs.user/52710>. Please
give me a sanity check. The scenario is my ligand is buried in a
hydrophobic cleft of the protein.

Thank you

On Wed, Nov 23, 2016 at 1:51 AM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 11/22/16 6:46 AM, abhisek Mondal wrote:
>
>> Hi,
>> I'm running the umbrella sampling code for the very first time for
>> protein-ligand system. My goal is to observe how the protein's
>> conformation
>> behaves when I pull the ligand and measure parameters subsequently.
>>
>> The pull code I've been using is:
>> ; Pull code
>> pull                    = yes
>> pull_ngroups            = 2
>> pull_ncoords            = 1
>> pull_group1_name        = JZ4
>> pull_group2_name        = Protein_chain_A
>> pull_coord1_type        = umbrella      ; harmonic biasing force
>> pull_coord1_geometry    = distance      ; simple distance increase
>> pull_coord1_groups      = 1 2
>> pull_coord1_dim         = N N Y
>> pull_coord1_rate        = 0.01          ; 0.01 nm per ps = 10 nm per ns
>> pull_coord1_k           = 500           ; kJ mol^-1 nm^-2
>> pull_coord1_start       = yes           ; define initial COM distance > 0
>>
>> Things are becoming bit hazy while I'm going for indexing. As per tutorial
>> the following guidelines are given:
>>
>> gmx make_ndx -f npt.gro
>> (> indicates the make_ndx prompt)
>>
>>> r 1-27
>>> name 19 Chain_A
>>> r 28-54
>>> name 20 Chain_B
>>> q
>>>
>>
>> But can you please help me indexing my system here. I'm not being able to
>> corroborate my system with the given code above.
>>
>> The output of "gmx make_ndx -f npt.gro" is:
>>
>>    1 MET     2 ASN     3 ILE     4 PHE     5 GLU     6 MET     7 LEU     8
>> ARG     9 ILE    10 ASP    11 GLU    12 GLY    13 LEU    14 ARG    15 LEU
>>  16 LYS    17 ILE    18 TYR    19 LYS    20 ASP    21 THR    22 GLU    23
>> GLY    24 TYR    25 TYR    26 THR    27 ILE    28 GLY    29 ILE    30 GLY
>>  31 HIS    32 LEU    33 LEU    34 THR    35 LYS    36 SER    37 PRO    38
>> ASP    39 LEU    40 ASN    41 ALA    42 ALA    43 LYS    44 SER    45 GLU
>>  46 LEU    47 ASP    48 LYS    49 ALA    50 ILE    51 GLY    52 ARG    53
>> ASN    54 CYS    55 ASN    56 GLY    57 VAL    58 ILE    59 THR    60 LYS
>>  61 ASP    62 GLU    63 ALA    64 GLU    65 LYS    66 LEU    67 PHE    68
>> ASN    69 GLN    70 ASP    71 VAL    72 ASP    73 ALA    74 ALA    75 VAL
>>  76 ARG    77 GLY    78 ILE    79 LEU    80 ARG    81 ASN    82 ALA    83
>> LYS    84 LEU    85 LYS    86 PRO    87 VAL    88 TYR    89 ASP    90 SER
>>  91 LEU    92 ASP    93 ALA    94 VAL    95 ARG    96 ARG    97 CYS    98
>> ALA    99 ALA   100 ILE   101 ASN   102 GLN   103 VAL   104 PHE   105 GLN
>> 106 MET   107 GLY   108 GLU   109 THR   110 GLY   111 VAL   112 ALA   113
>> GLY   114 PHE   115 THR   116 ASN   117 SER   118 LEU   119 ARG   120 MET
>> 121 LEU   122 GLN   123 GLN   124 LYS   125 ARG   126 TRP   127 ASP   128
>> GLU   129 ALA   130 ALA   131 VAL   132 ASN   133 LEU   134 ALA   135 LYS
>> 136 SER   137 ARG   138 TRP   139 TYR   140 ASN   141 GLN   142 THR   143
>> PRO   144 ASP   145 ARG   146 ALA   147 LYS   148 ARG   149 VAL   150 ILE
>> 151 THR   152 THR   153 PHE   154 ARG   155 THR   156 GLY   157 THR   158
>> TRP   159 ASP   160 ALA   161 TYR   162 LYS   163 ASN   164 JZ4    165 -
>> 10482 SOL     10483 - 10503 NA      10504 - 10530 CL
>>
>> Little help regarding the would be very nice.
>>
>>
> You have to define a sensible reaction coordinate between the protein and
> ligand based on the structural characteristics of the binding site, how
> occluded it is, whether there may be multiple paths, etc.  Typically a
> reference group is a residue or set of residue with which the ligand
> interacts.  The path is then set by the pulling vector based on the
> geometry of the system.
>
> -Justin
>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==================================================
>
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-- 
Abhisek Mondal

*Research Fellow*

*Structural Biology and Bioinformatics Division*
*CSIR-Indian Institute of Chemical Biology*

*Kolkata 700032*

*INDIA*


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