Hi,<div><br></div><div>We're trying to do absolute binding free energy calculations using Michael Shirts' latest free energy code (to be included in 4.6 if I understand correctly; right now it's a branch of 4.5). These require using a restraint between the protein and the ligand, which currently we're doing using virtual sites. I am interested in also doing these calculations using "decoupling", wherein internal interactions of the perturbed molecule (in this case the ligand) are retained. This involves something like the following in the mdp file:</div>
<div><br></div><div><meta charset="utf-8"><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; ">couple-moltype = MOL<br>couple-lambda0 = vdw-coul<br>
couple-lambda1 = none<br></span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; ">couple-intramol = no</span></div><div><font class="Apple-style-span" face="arial, sans-serif"><span class="Apple-style-span" style="border-collapse: collapse;"><br>
</span></font></div><div><font class="Apple-style-span" face="arial, sans-serif"><span class="Apple-style-span" style="border-collapse: collapse;">if, for example, the ligand is a molecule named 'MOL'.<br clear="all">
</span></font></div><div><font class="Apple-style-span" face="arial, sans-serif"><span class="Apple-style-span" style="border-collapse: collapse;"><br></span></font></div><div><font class="Apple-style-span" face="arial, sans-serif"><span class="Apple-style-span" style="border-collapse: collapse;">My question is this: Is there any way to get this to work when the ligand and the protein are part of the same "molecule"? Specifically, to have restraints betweeen the protein and the ligand (such as using a virtual site) which are NECESSARY for absolute binding free energy calculations, I must have the protein and ligand as part of the same molecule (unless there's a workaround I'm not aware of). But to get decoupling to work using the above I seem to need to have the protein and ligand as separate molecules, suggesting they are incompatible. Is there a workaround I'm not aware of?</span></font></div>
<div><br></div><div>Also, on a related note -- when decoupling is done, what is the end state for the decoupled object? Is it the decoupled object in gas phase in a periodic system (interacting with copies of itself), or in a nonperiodic system? </div>
<div><br></div><div>Thanks!</div><div><br></div><div>-- </div><div>David Mobley<br><a href="mailto:dmobley@gmail.com" target="_blank">dmobley@gmail.com</a><br>504-383-3662<br><br><br>
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