[gmx-users] protein-ligand umbrella sampling

[Justin Lemkul]

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

==================================================