Re: [GaMD-discuss] PPI-GaMD igamd=17 potential statistics = 0
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Re: [GaMD-discuss] PPI-GaMD igamd=17 potential statistics = 0
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From: Miao, Y. <Yin...@me...> - 2025-05-23 18:24:47
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Hi Irene, I’m glad you debugged an issue! I have two additional questions: first of all, in order to set the best sigma value, one should just check that the k_0 reaches 1, without having high sigma_DeltaV, therefore, if one uses the lower bound condition, when k_0 reaches 1, increasing the sigma value, while keeping sigma_DeltaV < 10k_BT, does not have any effect on the potential boost, am I right? Therefore, one should keep the sigma to the minimum value allowing to reach k_0 = 1 to have a proper reweighing, right? Right. And normally the default values of sigma0 should be able to make k0 reach 1 before the end of GaMD equilibration. My second question actually concerns the timask1, scmask1 parameters with igamd=16 or 17: if the protein is big and the atom limit is overcome, would it be possible to specify a subset of atoms (i.e. backbone atoms)? No, since you want to boot the non-bonded interaction energy, all related atoms need to be selected. Jinan in our lab came up a fix for the atom limit issue: https://www.med.unc.edu/pharm/miaolab/conferences/gamd2024/faq/ Q: How to fix limitation of the maximum number of TI atoms for running PPI-GaMD simulations? A: To address the limitation on the maximum number of TI atoms, adjust the MaxNumberTIAtom parameter in the ${AMBERHOME}/src/pmemd/src/gti_controlVariable.i file. Increase MaxNumberTIAtom to a value that exceeds the maximum number of TI atoms specified in TIMASK1 and SCMASK1, according to your system’s requirements. After making these adjustments, recompile the AMBER24 code with the updated gti_controlVariable.i file. Hope this helps, Yinglong Yinglong Miao, Ph.D. Associate Professor Department of Pharmacology and Computational Medicine Program University of North Carolina - Chapel Hill Tel: 1-919-962-5696 http://miaolab.org<http://miaolab.org/> Editor-in-Chief npj Drug Discovery https://www.nature.com/npjdrugdiscov On May 22, 2025, at 3:18 AM, Irene Maffucci <ire...@ut...> wrote: Hello Yinglong, I checked my input file and I have actually made a mistake in the timask1, thank you for letting me notice it! I have two additional questions: first of all, in order to set the best sigma value, one should just check that the k_0 reaches 1, without having high sigma_DeltaV, therefore, if one uses the lower bound condition, when k_0 reaches 1, increasing the sigma value, while keeping sigma_DeltaV < 10k_BT, does not have any effect on the potential boost, am I right? Therefore, one should keep the sigma to the minimum value allowing to reach k_0 = 1 to have a proper reweighing, right? My second question actually concerns the timask1, scmask1 parameters with igamd=16 or 17: if the protein is big and the atom limit is overcome, would it be possible to specify a subset of atoms (i.e. backbone atoms)? Thanks in advance for the help Best Irene --------------------------------------------------------------------- Irene Maffucci, PhD Lab. de Génie Enzymatique et Cellulaire UMR 7025 Université de technologie de Compiègne Centre de Recherche Royallieu CS60319 60203 Compiègne cedex Tel. +33 (0)3 44 23 43 42 Le 22 mai 2025 à 03:07, Miao, Yinglong <Yin...@me...> a écrit : Hi Irene, Great that you observed unbinding/binding events of the oligonucleotide in your simulations! As you read about the PPI-GaMD algorithm, it applies selective boost potential to the non-bonded interaction potential energy of two binding partners, which can be proteins and probably other biomolecules of your interest like protein-oligonucleotide. I guess it’s only a naming issue here. With igamd=17, the dual-boost mode is indeed turned on. You may want to double check if parameters such as timask1, scmask1, bgpro2atm and edpro2atm are set properly so that the boosted potential energies are calculated correctly. If you can perhaps share a copy of the mdout file for the “Equilibration” part, we can look into the issue more. Best, Yinglong Yinglong Miao, Ph.D. Associate Professor Department of Pharmacology and Computational Medicine Program University of North Carolina - Chapel Hill Tel: 1-919-962-5696 http://miaolab.org<http://miaolab.org/> Editor-in-Chief npj Drug Discovery https://www.nature.com/npjdrugdiscov On May 20, 2025, at 10:00 AM, Irene Maffucci <ire...@ut...> wrote: Hello everyone, I am running PPI-GaMD on a protein-oligonucleotide complex. First of all, although PPI-GaMD has been developed for PPIs, can it be applied also on the kind of complex I am simulating? I am observing unbinding/binding events of the oligonucleotide, but I would like to know your opinion about the suitability of GaMD for these systems. I am running my simulations with Amber by setting igamd=17, with therefore a dual boost. However, when I give a look at the log files I have the statistics for VmaxD, VminD, VavgD, sigmaVD, but all the statistics for the VmaxP, VminP, VavgP and sigmaVP are 0. Is this normal? In addition, for the choice of the sigma0 values, I let them to 6 kcal/mol and I verified that the k0 reached 1, but I observe a large sigmaVD. What should I do in this case? Thanks and best regards Irene --------------------------------------------------------------------- Irene Maffucci, PhD Lab. de Génie Enzymatique et Cellulaire UMR 7025 Université de technologie de Compiègne Centre de Recherche Royallieu CS60319 60203 Compiègne cedex Tel. +33 (0)3 44 23 43 42 _______________________________________________ GaMD-discuss mailing list GaM...@li... https://lists.sourceforge.net/lists/listinfo/gamd-discuss |
