Re: [gmx-users] temperature variation of all-atom CHARMM force fields
Hi, You could also observe the change in e.g. free-energy of solvation of that ion in that force field upon change in temperature. Or maybe something even more relevant? Mark On Thu, Jul 2, 2015 at 5:29 PM Justin Lemkul jalem...@vt.edu wrote: On 7/2/15 10:33 AM, soumadwip ghosh wrote: Hi, I am stuck with one of the reviews of my paper where i have investigated the thermodynamics of small molecular ion binding to DNA duplex using CHARMM 27 force field. In order to do so I calculated the PMF of the binding processes at different temperature ( 300, 270 and 330K) and then decomposed the temperature dependent PMFs to estimate the entropy and enthalpy contributions respectively. One of the reviewer has strong objection about the validation of classical force fields beyond room temperature. While I know this has been a major issue in simulation of biomolecules (say temperature assisted protein unfolding or hydrophobic interactions between two methane molecules in water) and REMD may be a possible way out but there are examples of works such as below where temperature variation of force fields during a classical MD simulation did not seem to be an issue or neither has been addressed by the authors. http://pubs.acs.org/doi/pdf/10.1021/jp056909r and http://pubs.acs.org/doi/pdf/10.1021/jp512336n I cannot perform REMD for all the ion associations at this moment and apart from this comment I have satisfactorily answered the rest of the queries of the referees. Is there some way by which I can convince the referee? Can anyone help me with some references where CHARMM force fields have been used without any modification to study a biomolecule beyond room temperature using MD simulations? In general I will be highly obliged if someone helps me with an appropriate response to the reviewer? There have been DNA base flipping studies that have done this, though I don't remember if it was with CHARMM or AMBER. In any case, an objection about 330 K strikes me as pretty absurd. That's not an unreasonable temperature, and people simulate membrane proteins in DPPC at 323 K or higher all the time and they're fine. You start getting into trouble at 400, 500 K, etc. -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 jalem...@outerbanks.umaryland.edu | (410) 706-7441 http://mackerell.umaryland.edu/~jalemkul == -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
[gmx-users] temperature variation of all-atom CHARMM force fields
Hi, I am stuck with one of the reviews of my paper where i have investigated the thermodynamics of small molecular ion binding to DNA duplex using CHARMM 27 force field. In order to do so I calculated the PMF of the binding processes at different temperature ( 300, 270 and 330K) and then decomposed the temperature dependent PMFs to estimate the entropy and enthalpy contributions respectively. One of the reviewer has strong objection about the validation of classical force fields beyond room temperature. While I know this has been a major issue in simulation of biomolecules (say temperature assisted protein unfolding or hydrophobic interactions between two methane molecules in water) and REMD may be a possible way out but there are examples of works such as below where temperature variation of force fields during a classical MD simulation did not seem to be an issue or neither has been addressed by the authors. http://pubs.acs.org/doi/pdf/10.1021/jp056909r and http://pubs.acs.org/doi/pdf/10.1021/jp512336n I cannot perform REMD for all the ion associations at this moment and apart from this comment I have satisfactorily answered the rest of the queries of the referees. Is there some way by which I can convince the referee? Can anyone help me with some references where CHARMM force fields have been used without any modification to study a biomolecule beyond room temperature using MD simulations? In general I will be highly obliged if someone helps me with an appropriate response to the reviewer? Sorry if I am asking for much. Thank you for your time in advance. Regards Soumadwip Ghosh Research Fellow IITB India -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] temperature variation of all-atom CHARMM force fields
On 7/2/15 10:33 AM, soumadwip ghosh wrote: Hi, I am stuck with one of the reviews of my paper where i have investigated the thermodynamics of small molecular ion binding to DNA duplex using CHARMM 27 force field. In order to do so I calculated the PMF of the binding processes at different temperature ( 300, 270 and 330K) and then decomposed the temperature dependent PMFs to estimate the entropy and enthalpy contributions respectively. One of the reviewer has strong objection about the validation of classical force fields beyond room temperature. While I know this has been a major issue in simulation of biomolecules (say temperature assisted protein unfolding or hydrophobic interactions between two methane molecules in water) and REMD may be a possible way out but there are examples of works such as below where temperature variation of force fields during a classical MD simulation did not seem to be an issue or neither has been addressed by the authors. http://pubs.acs.org/doi/pdf/10.1021/jp056909r and http://pubs.acs.org/doi/pdf/10.1021/jp512336n I cannot perform REMD for all the ion associations at this moment and apart from this comment I have satisfactorily answered the rest of the queries of the referees. Is there some way by which I can convince the referee? Can anyone help me with some references where CHARMM force fields have been used without any modification to study a biomolecule beyond room temperature using MD simulations? In general I will be highly obliged if someone helps me with an appropriate response to the reviewer? There have been DNA base flipping studies that have done this, though I don't remember if it was with CHARMM or AMBER. In any case, an objection about 330 K strikes me as pretty absurd. That's not an unreasonable temperature, and people simulate membrane proteins in DPPC at 323 K or higher all the time and they're fine. You start getting into trouble at 400, 500 K, etc. -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 jalem...@outerbanks.umaryland.edu | (410) 706-7441 http://mackerell.umaryland.edu/~jalemkul == -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
