ADL: High Torsional Free energy of ligand - please help

Guili Zhu liebely at gmail.com
Tue Nov 13 10:11:20 PST 2007


Dear AutoDockers,

May I have your attention for a problem that occurred during my dock,
please?

When analyzing my *.dlg file, i realized that all the bound conformations
had high positive binding energy. It seems to be due to the initial high
torsional free energy of the unbound ligand:

Calculating normalized torsion vectors.

Number of atoms in ligand:  131

Number of vibrational degrees of freedom of ligand:  387


Number of torsional degrees of freedom = 90
Estimated loss of torsional free energy upon binding = +24.6960 kcal/mol


As a result of this, the docked energy of all conformations are like this:

DOCKED: MODEL       47
DOCKED: USER    Run = 47
DOCKED: USER    DPF = 26m1LA_hbb50.dpf
DOCKED: USER
DOCKED: USER    Estimated Free Energy of Binding    =  +20.19 kcal/mol
[=(1)+(2)+
(3)-(4)]
DOCKED: USER
DOCKED: USER    (1) Final Intermolecular Energy     =   -6.74 kcal/mol
DOCKED: USER        vdW + Hbond + desolv Energy     =   -6.85 kcal/mol
DOCKED: USER        Electrostatic Energy            =   +0.11 kcal/mol
DOCKED: USER    (2) Final Total Internal Energy     =   -6.33 kcal/mol
DOCKED: USER    (3) Torsional Free Energy           =  +24.70 kcal/mol
DOCKED: USER    (4) Unbound System's Energy         =   -8.56 kcal/mol


Could you specialists let me know how to solve this? Should I do energy
minimization of the ligand?
 If so, what energy minimization program is compatible with structures
containing rotatable bonds in .pdbqt format?
 If not, what else can I do??

Looking forward to your reply! Many thanks!

regards,
guili

p.s.: My ligand is a amphiphilic molecule containg two connected sugar rings
with phosphate groups attached to each, and with multiple acyl chains
attached to each ring (thus extremely flexible).


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