Dear Gromacs Users, I am trying to find out the relative free energy difference of binding of a ligand with wild type protein (Glutamate residue) and mutant protein (Alanine residue).
For charge part of the mutation, this is what I'm planning to do: ; residue 40 GLU rtp GLU q -1.0 552 opls_238 40 GLU N 191 -0.5 14.0067 opls_238 -0.5 14.0067 ; qtot 0.5 553 opls_241 40 GLU H 191 0.3 1.008 opls_241 0.3 1.008 ; qtot 0.8 554 opls_224B 40 GLU CA 191 0.14 12.011 opls_224B 0.14 12.011 ; qtot 0.94 555 opls_140 40 GLU HA 191 0.06 1.008 opls_140 0.06 1.008 ; qtot 1 556 opls_136 40 GLU CB 192 -0.12 12.011 opls_135 -0.18 12.011 ; qtot 0.88 557 opls_140 40 GLU HB1 192 0.06 1.008 opls_140 0.06 1.008 ; qtot 0.94 558 opls_140 40 GLU HB2 192 0.06 1.008 opls_140 0.06 1.008 ; qtot 1 559 opls_274 40 GLU CG 193 -0.22 12.011 opls_140 0.06 1.008 ; qtot 0.78 560 opls_140 40 GLU HG1 193 0.06 1.008 DUM_140 0.0 1.008 ; qtot 0.84 561 opls_140 40 GLU HG2 193 0.06 1.008 DUM_140 0.0 1.008 ; qtot 0.9 562 opls_271 40 GLU CD 194 0.7 12.011 DUM_271 0.0 12.011 ; qtot 1.6 563 opls_272 40 GLU OE1 194 -0.8 15.9994 DUM_272 0.0 15.9994 ; qtot 0.8 564 opls_272 40 GLU OE2 194 -0.8 15.9994 DUM_272 0.0 15.9994 ; qtot 0 565 opls_235 40 GLU C 195 0.5 12.011 opls_235 0.5 12.011 ; qtot 0.5 566 opls_236 40 GLU O 195 -0.5 15.9994 opls_236 -0.5 15.9994 ; qtot 0 I added the DUM_140, DUM_271,DUM_272 atomtypes in ffnonbonded.itp. Further I added the bondtypes, angletypes and dihedraltypes in ffbonded.itp for state B. In order to maintain the electroneutrality, I am mutating a K+ ion to dummy as well. For the K+ going to dummy, I added a DUM_408 atomtype as well. *The questions I have are as follows:* *During the charge mutation will my dummy atoms have sigma and epsilon as 0.0? Since Ala residue does not have Cgamma, Cdelta and the oxygen as well as the Hgamma, all the dummy atoms should have sigma and epsilon as zero. Am I correct for this assumption?* *Further as I am mutating one ion, I dont want the mutating ion to come close to other ions (I have three K+ ions as my protein has -3 charge) as well as the protein atoms. Hence I'm having position restraints on the three ions. * *For the ion that is mutating to dummy, should I have have position restraints on dummy atom as well for the B state topology?* The section of topology for the K+ going to dummy is as follows: [ moleculetype ] ; Name nrexcl KM 1 [ atoms ] ; nr type resnr residue atom cgnr charge mass typeB chargeB massB 1 opls-408 1 KM KM 1 1 39.0983 DUM_408 0.0 39.0983 #ifdef POSRES_ION ; Position restraint for each Potassium ion [ position_restraints ] ; i funct fcx fcy fcz 1 1 1000 1000 1000 0 0 0 #endif Here I defined the KM as K+ that will go to dummy and other two K+ ions are represented as regular K+ ions. I'm pasting the regular K+ ion part of the topology below. [ moleculetype ] ; Name nrexcl K 1 [ atoms ] ; nr type resnr residue atom cgnr charge mass typeB chargeB massB 1 opls_408 1 K K 1 1 39.0983 #ifdef POSRES_ION ; Position restraint for each Potassium ion [ position_restraints ] ; i funct fcx fcy fcz 1 1 1000 1000 1000 #endif Let me know if you need more information. Thanks for your time, Regards Sai
-- gmx-users mailing list gmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists