Re: [gmx-users] RE: Gibbs free energy of binding
Ok.you are right,actually entropy has contribution as H,of course it seems to me! On Sun, Oct 24, 2010 at 9:32 PM, wrote: > Mohsen, > > Writing H as E+PV does not change the nature of my question. It was said > that when computing binding Delta Delta G between two close variants, most > entropic contributions would tend to cancel. My question is why, when there > are many components to the gibbs free energy, would some components (stated > as entropy) cancel in a delta delta G while some are not expected to cancel > (implicitly taken to be enthalpy or internal energy or pressure volume > work). And also, is this a hunch or has it been shown? > > Thanks, > Chris. > > > -- original message -- > > Dear Chris > Do you mean Gibbs free energy? > there are a general relation in statistical mechanics as below: > G=E-TS+PV > in this relation E is internal energy and S is entropy,then enthalepy is > not > comming in relation anywhere, > besides there are not any reason for canceling G when Del Del S is canceled > > On Sun, Oct 24, 2010 at 9:04 PM, wrote: > > Ehud, >> >> when computing binding Delta Delta G between two close variants, why would >> entropy tend to cancel and enthalpy not tend to cancel? Even in the case >> of >> small perturbations, this sounds like wishful thinking to me ;) >> >> Chris. >> >> -- original message -- >> >> Hi Moshen, >> >> I think everybody agrees that a full calculation such as Free Energy >> Perturbation is the accurate, if difficult and lengthy, approach. >> The entropic effects usually cannot simply be ignored. All I tried to >> say was that there are approximation schemes for these (see the >> reference below). Still, I would trust such approximations only when >> computing binding Delta Delta G between two close variants (e.g. a wild >> type protein and a one residue mutation) such that - >> > > > -- > gmx-users mailing listgmx-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 thewww interface > or send it to gmx-users-requ...@gromacs.org. > Can't post? Read http://www.gromacs.org/Support/Mailing_Lists > -- gmx-users mailing listgmx-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
[gmx-users] RE: Gibbs free energy of binding
Mohsen, Writing H as E+PV does not change the nature of my question. It was said that when computing binding Delta Delta G between two close variants, most entropic contributions would tend to cancel. My question is why, when there are many components to the gibbs free energy, would some components (stated as entropy) cancel in a delta delta G while some are not expected to cancel (implicitly taken to be enthalpy or internal energy or pressure volume work). And also, is this a hunch or has it been shown? Thanks, Chris. -- original message -- Dear Chris Do you mean Gibbs free energy? there are a general relation in statistical mechanics as below: G=E-TS+PV in this relation E is internal energy and S is entropy,then enthalepy is not comming in relation anywhere, besides there are not any reason for canceling G when Del Del S is canceled On Sun, Oct 24, 2010 at 9:04 PM, wrote: Ehud, when computing binding Delta Delta G between two close variants, why would entropy tend to cancel and enthalpy not tend to cancel? Even in the case of small perturbations, this sounds like wishful thinking to me ;) Chris. -- original message -- Hi Moshen, I think everybody agrees that a full calculation such as Free Energy Perturbation is the accurate, if difficult and lengthy, approach. The entropic effects usually cannot simply be ignored. All I tried to say was that there are approximation schemes for these (see the reference below). Still, I would trust such approximations only when computing binding Delta Delta G between two close variants (e.g. a wild type protein and a one residue mutation) such that - -- gmx-users mailing listgmx-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
Re: [gmx-users] RE: Gibbs free energy of binding
Dear Chris Do you mean Gibbs free energy? there are a general relation in statistical mechanics as below: G=E-TS+PV in this relation E is internal energy and S is entropy,then enthalepy is not comming in relation anywhere, besides there are not any reason for canceling G when Del Del S is canceled On Sun, Oct 24, 2010 at 9:04 PM, wrote: > Ehud, > > when computing binding Delta Delta G between two close variants, why would > entropy tend to cancel and enthalpy not tend to cancel? Even in the case of > small perturbations, this sounds like wishful thinking to me ;) > > Chris. > > -- original message -- > > Hi Moshen, > > I think everybody agrees that a full calculation such as Free Energy > Perturbation is the accurate, if difficult and lengthy, approach. > The entropic effects usually cannot simply be ignored. All I tried to > say was that there are approximation schemes for these (see the > reference below). Still, I would trust such approximations only when > computing binding Delta Delta G between two close variants (e.g. a wild > type protein and a one residue mutation) such that most entropic > contributions would tend to cancel. > > Ehud. > > > > > -- > gmx-users mailing listgmx-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 thewww interface > or send it to gmx-users-requ...@gromacs.org. > Can't post? Read http://www.gromacs.org/Support/Mailing_Lists > -- gmx-users mailing listgmx-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
[gmx-users] RE: Gibbs free energy of binding
Ehud, when computing binding Delta Delta G between two close variants, why would entropy tend to cancel and enthalpy not tend to cancel? Even in the case of small perturbations, this sounds like wishful thinking to me ;) Chris. -- original message -- Hi Moshen, I think everybody agrees that a full calculation such as Free Energy Perturbation is the accurate, if difficult and lengthy, approach. The entropic effects usually cannot simply be ignored. All I tried to say was that there are approximation schemes for these (see the reference below). Still, I would trust such approximations only when computing binding Delta Delta G between two close variants (e.g. a wild type protein and a one residue mutation) such that most entropic contributions would tend to cancel. Ehud. -- gmx-users mailing listgmx-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
Re: [gmx-users] RE: Gibbs free energy of binding
Ehud Schreiber wrote: Hi Moshen, I think everybody agrees that a full calculation such as Free Energy Perturbation is the accurate, if difficult and lengthy, approach. Wouldn't convergence of such a system be a major issue with a method like FEP? I think PMF would be the better option here. It would still require significant data collection, but I think it would be easier to get usable data. -Justin The entropic effects usually cannot simply be ignored. All I tried to say was that there are approximation schemes for these (see the reference below). Still, I would trust such approximations only when computing binding Delta Delta G between two close variants (e.g. a wild type protein and a one residue mutation) such that most entropic contributions would tend to cancel. Ehud. -- Date: Thu, 21 Oct 2010 22:45:23 +0330 From: mohsen ramezanpour Subject: Re: [gmx-users] RE: Gibbs free energy of binding reading your idea: it seems to me I can't ignore entropy contribution because my simulation is at room tempreture. Really I couldn't understand what can I do! I am working at room tempreture and I want to estimate binding free energy(delta G),can I ignore entropy in this simulation and calculate binding free energy by the method that I said in my last email? what do you think? thank in advance for your guid On Thu, Oct 21, 2010 at 12:15 PM, David van der Spoel wrote: On 2010-10-21 10.39, Ehud Schreiber wrote: Actually, I believe that using the energy difference, Delta E, as an approximation to the free energy difference, Delta G, is a valid approach (which I'm considering myself). The entropic contribution to Delta G, namely -T Delta S, may be less prominent than Delta E. In addition, Delta S can be approximated by various means - see e.g. Doig& Sternberg 1995. I understand that such an approach is utilized in the Accelrys Discovery Studio. Obviously, this is an approximation that might be too crude for some applications. -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin -- gmx-users mailing listgmx-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
[gmx-users] RE: Gibbs free energy of binding
Hi Moshen, I think everybody agrees that a full calculation such as Free Energy Perturbation is the accurate, if difficult and lengthy, approach. The entropic effects usually cannot simply be ignored. All I tried to say was that there are approximation schemes for these (see the reference below). Still, I would trust such approximations only when computing binding Delta Delta G between two close variants (e.g. a wild type protein and a one residue mutation) such that most entropic contributions would tend to cancel. Ehud. -- Date: Thu, 21 Oct 2010 22:45:23 +0330 From: mohsen ramezanpour Subject: Re: [gmx-users] RE: Gibbs free energy of binding >reading your idea: >it seems to me I can't ignore entropy contribution because my simulation is >at room tempreture. >Really I couldn't understand what can I do! >I am working at room tempreture and I want to estimate binding free >energy(delta G),can I ignore entropy in this simulation and calculate >binding free energy by the method that I said in my last email? >what do you think? >thank in advance for your guid On Thu, Oct 21, 2010 at 12:15 PM, David van der Spoel wrote: > On 2010-10-21 10.39, Ehud Schreiber wrote: > >> Actually, I believe that using the energy difference, Delta E, as an >> approximation to the free energy difference, Delta G, is a valid >> approach (which I'm considering myself). The entropic contribution to >> Delta G, namely -T Delta S, may be less prominent than Delta E. >> In addition, Delta S can be approximated by various means - see e.g. >> Doig& Sternberg 1995. I understand that such an approach is utilized in >> the Accelrys Discovery Studio. >> Obviously, this is an approximation that might be too crude for some >> applications. >> > -- gmx-users mailing listgmx-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
Re: [gmx-users] RE: Gibbs free energy of binding
reading your idea: it seems to me I can't ignore entropy contribution because my simulation is at room tempreture. Really I couldn't understand what can I do! I am working at room tempreture and I want to estimate binding free energy(delta G),can I ignore entropy in this simulation and calculate binding free energy by the method that I said in my last email? what do you think? thank in advance for your guid On Thu, Oct 21, 2010 at 10:45 PM, mohsen ramezanpour < ramezanpour.moh...@gmail.com> wrote: > reading your idea: > it seems to me I can't ignore entropy contribution because my simulation > is at room tempreture. > Really I couldn't understand what can I do! > I am working at room tempreture and I want to estimate binding free > energy(delta G),can I ignore entropy in this simulation and calculate > binding free energy by the method that I said in my last email? > what do you think? > thank in advance for your guid > > > > On Thu, Oct 21, 2010 at 12:15 PM, David van der Spoel < > sp...@xray.bmc.uu.se> wrote: > >> On 2010-10-21 10.39, Ehud Schreiber wrote: >> >>> Actually, I believe that using the energy difference, Delta E, as an >>> approximation to the free energy difference, Delta G, is a valid >>> approach (which I'm considering myself). The entropic contribution to >>> Delta G, namely -T Delta S, may be less prominent than Delta E. >>> In addition, Delta S can be approximated by various means - see e.g. >>> Doig& Sternberg 1995. I understand that such an approach is utilized in >>> the Accelrys Discovery Studio. >>> Obviously, this is an approximation that might be too crude for some >>> applications. >>> >> >> As a simple example the hydrophobic effect at room temperature is largely >> due to the entropy of the water [ at high temp it is due to the enthalpy of >> the water ]. >> >> Since the hydrophobic effect is involved in all ligand binding it seems >> quite hopeless to get any reliable numbers when neglecting entropy. No >> referee will buy that - I wouldn't. >> >> >> >>> What do you think? >>> >>> >>> -- >>> >>> On Oct 21, 2010, at 09:25 , Sander Pronk wrote: >>> >>> Hi Mohsen, >>> >>> The mean energy difference is only one component of the free energy >>> difference. >>> >>> Before you go any further I'd suggest reading a good book on molecular >>> simulations, like 'Understanding Molecular Simulations' by Frenkel and >>> Smit. >>> >>> There's a good reason free energy calculations cover over half of that >>> book. >>> >>> Sander >>> >>> >>> On Oct 21, 2010, at 09:18 , mohsen ramezanpour wrote: >>> >>> Dear Justin If I do two MD simulations for a short time in the same >>> conditions(of course separately for protein and drug) >>> and calculate total energy of each one and sum them with each other >>> as E1 as nonbonding free energy of system. >>> then a MD simulation for Protein-drug system in the same condition and >>> calculate it's total energy too as E2 as bound system . >>> what does (E1-E2)mean? I think it is binding free energy,Is not it? in the other hand when we are working on NPT ensamble it means Gibbs >>> free energy is the main energy and our total energy is equal to Gibbs >>> free energy. >>> Then,what is the problem? >>> >> >> -- >> David van der Spoel, Ph.D., Professor of Biology >> Dept. of Cell & Molec. Biol., Uppsala University. >> Box 596, 75124 Uppsala, Sweden. Phone: +46184714205. >> sp...@xray.bmc.uu.sehttp://folding.bmc.uu.se >> >> -- >> gmx-users mailing listgmx-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 >> > > -- gmx-users mailing listgmx-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
Re: [gmx-users] RE: Gibbs free energy of binding
reading your idea: it seems to me I can't ignore entropy contribution because my simulation is at room tempreture. Really I couldn't understand what can I do! I am working at room tempreture and I want to estimate binding free energy(delta G),can I ignore entropy in this simulation and calculate binding free energy by the method that I said in my last email? what do you think? thank in advance for your guid On Thu, Oct 21, 2010 at 12:15 PM, David van der Spoel wrote: > On 2010-10-21 10.39, Ehud Schreiber wrote: > >> Actually, I believe that using the energy difference, Delta E, as an >> approximation to the free energy difference, Delta G, is a valid >> approach (which I'm considering myself). The entropic contribution to >> Delta G, namely -T Delta S, may be less prominent than Delta E. >> In addition, Delta S can be approximated by various means - see e.g. >> Doig& Sternberg 1995. I understand that such an approach is utilized in >> the Accelrys Discovery Studio. >> Obviously, this is an approximation that might be too crude for some >> applications. >> > > As a simple example the hydrophobic effect at room temperature is largely > due to the entropy of the water [ at high temp it is due to the enthalpy of > the water ]. > > Since the hydrophobic effect is involved in all ligand binding it seems > quite hopeless to get any reliable numbers when neglecting entropy. No > referee will buy that - I wouldn't. > > > >> What do you think? >> >> >> -- >> >> On Oct 21, 2010, at 09:25 , Sander Pronk wrote: >> >> Hi Mohsen, >> >> The mean energy difference is only one component of the free energy >> difference. >> >> Before you go any further I'd suggest reading a good book on molecular >> simulations, like 'Understanding Molecular Simulations' by Frenkel and >> Smit. >> >> There's a good reason free energy calculations cover over half of that >> book. >> >> Sander >> >> >> On Oct 21, 2010, at 09:18 , mohsen ramezanpour wrote: >> >> Dear Justin >>> >>> If I do two MD simulations for a short time in the same >>> >> conditions(of course separately for protein and drug) >> >>> and calculate total energy of each one and sum them with each other >>> >> as E1 as nonbonding free energy of system. >> >>> then a MD simulation for Protein-drug system in the same condition and >>> >> calculate it's total energy too as E2 as bound system . >> >>> what does (E1-E2)mean? >>> I think it is binding free energy,Is not it? >>> in the other hand when we are working on NPT ensamble it means Gibbs >>> >> free energy is the main energy and our total energy is equal to Gibbs >> free energy. >> >>> Then,what is the problem? >>> >> > > -- > David van der Spoel, Ph.D., Professor of Biology > Dept. of Cell & Molec. Biol., Uppsala University. > Box 596, 75124 Uppsala, Sweden. Phone: +46184714205. > sp...@xray.bmc.uu.sehttp://folding.bmc.uu.se > > -- > gmx-users mailing listgmx-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 > -- gmx-users mailing listgmx-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
[gmx-users] RE: Gibbs free energy of binding
Hi, Under constant pressure a potential energy change is in many cases a good approximation for the change of enthalpy (if only small variations of volume are present). However, for many biomolecular applications, and in particular ligand binding, the entropy contribution cannot be neglected unless you compare two very similar reactions (e.g., delta delta G of binding of two protein inhibitors with similar structures). Examples on the size of T delta S are given in many publications discussing MM/PBSA and its variants - in the past we calculated absolute values that were in the same order of magnitude as delta G for a protein-peptide complex (http://dx.doi.org/10.1529/biophysj.106.085399). I'm not familiar with Material Studio, but there are several methods to calculate entropy changes from MD simulations - quasi harmonic analysis is one that's implemented in Gromacs and Wordom. All have their limitations, but the same is true for experimental measurements of entropy changes upon binding. Ran Ran Friedman Biträdande Lektor (Assistant Professor) Linnaeus University School of Natural Sciences 391 82 Kalmar, Sweden +46 480 44 6290 Telephone +46 76 207 8763 Mobile ran.fried...@lnu.se http://lnu.se/research-groups/computational-chemistry-and-biochemistry-group?l=en From: gmx-users-boun...@gromacs.org [gmx-users-boun...@gromacs.org] On Behalf Of Ehud Schreiber [schr...@compugen.co.il] Sent: 21 October 2010 10:39 To: gmx-users@gromacs.org Subject: [gmx-users] RE: Gibbs free energy of binding Actually, I believe that using the energy difference, Delta E, as an approximation to the free energy difference, Delta G, is a valid approach (which I'm considering myself). The entropic contribution to Delta G, namely -T Delta S, may be less prominent than Delta E. In addition, Delta S can be approximated by various means - see e.g. Doig & Sternberg 1995. I understand that such an approach is utilized in the Accelrys Discovery Studio. Obviously, this is an approximation that might be too crude for some applications. What do you think? -- On Oct 21, 2010, at 09:25 , Sander Pronk wrote: Hi Mohsen, The mean energy difference is only one component of the free energy difference. Before you go any further I'd suggest reading a good book on molecular simulations, like 'Understanding Molecular Simulations' by Frenkel and Smit. There's a good reason free energy calculations cover over half of that book. Sander On Oct 21, 2010, at 09:18 , mohsen ramezanpour wrote: > Dear Justin > > If I do two MD simulations for a short time in the same conditions(of course separately for protein and drug) > and calculate total energy of each one and sum them with each other as E1 as nonbonding free energy of system. > then a MD simulation for Protein-drug system in the same condition and calculate it's total energy too as E2 as bound system . > what does (E1-E2)mean? > I think it is binding free energy,Is not it? > in the other hand when we are working on NPT ensamble it means Gibbs free energy is the main energy and our total energy is equal to Gibbs free energy. > Then,what is the problem? -- gmx-users mailing listgmx-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 -- gmx-users mailing listgmx-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
Re: [gmx-users] RE: Gibbs free energy of binding
To put some numbers to what David said, here's an experimental paper on a well-studied drug-protein complex: http://pubs.acs.org/doi/pdf/10.1021/bi001013s the entropic contribution of HIV-1 protease inhibitor binding is about 3x bigger than the enthalpic contribution for all 4 drugs studied there. I'm not sure if that's a special case, but if you're leaving out entropy you are at the very least doing an uncontrolled approximation - you don't know how big the term is you're missing, and it could be the dominant term. Sander On 21 Oct 2010, at 10:45 , David van der Spoel wrote: > On 2010-10-21 10.39, Ehud Schreiber wrote: >> Actually, I believe that using the energy difference, Delta E, as an >> approximation to the free energy difference, Delta G, is a valid >> approach (which I'm considering myself). The entropic contribution to >> Delta G, namely -T Delta S, may be less prominent than Delta E. >> In addition, Delta S can be approximated by various means - see e.g. >> Doig& Sternberg 1995. I understand that such an approach is utilized in >> the Accelrys Discovery Studio. >> Obviously, this is an approximation that might be too crude for some >> applications. > > As a simple example the hydrophobic effect at room temperature is largely due > to the entropy of the water [ at high temp it is due to the enthalpy of the > water ]. > > Since the hydrophobic effect is involved in all ligand binding it seems quite > hopeless to get any reliable numbers when neglecting entropy. No referee will > buy that - I wouldn't. > >> >> What do you think? >> >> >> -- >> >> On Oct 21, 2010, at 09:25 , Sander Pronk wrote: >> >> Hi Mohsen, >> >> The mean energy difference is only one component of the free energy >> difference. >> >> Before you go any further I'd suggest reading a good book on molecular >> simulations, like 'Understanding Molecular Simulations' by Frenkel and >> Smit. >> >> There's a good reason free energy calculations cover over half of that >> book. >> >> Sander >> >> >> On Oct 21, 2010, at 09:18 , mohsen ramezanpour wrote: >> >>> Dear Justin >>> >>> If I do two MD simulations for a short time in the same >> conditions(of course separately for protein and drug) >>> and calculate total energy of each one and sum them with each other >> as E1 as nonbonding free energy of system. >>> then a MD simulation for Protein-drug system in the same condition and >> calculate it's total energy too as E2 as bound system . >>> what does (E1-E2)mean? >>> I think it is binding free energy,Is not it? >>> in the other hand when we are working on NPT ensamble it means Gibbs >> free energy is the main energy and our total energy is equal to Gibbs >> free energy. >>> Then,what is the problem? > > > -- > David van der Spoel, Ph.D., Professor of Biology > Dept. of Cell & Molec. Biol., Uppsala University. > Box 596, 75124 Uppsala, Sweden. Phone:+46184714205. > sp...@xray.bmc.uu.sehttp://folding.bmc.uu.se > -- > gmx-users mailing listgmx-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 -- gmx-users mailing listgmx-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
Re: [gmx-users] RE: Gibbs free energy of binding
On 2010-10-21 10.39, Ehud Schreiber wrote: Actually, I believe that using the energy difference, Delta E, as an approximation to the free energy difference, Delta G, is a valid approach (which I'm considering myself). The entropic contribution to Delta G, namely -T Delta S, may be less prominent than Delta E. In addition, Delta S can be approximated by various means - see e.g. Doig& Sternberg 1995. I understand that such an approach is utilized in the Accelrys Discovery Studio. Obviously, this is an approximation that might be too crude for some applications. As a simple example the hydrophobic effect at room temperature is largely due to the entropy of the water [ at high temp it is due to the enthalpy of the water ]. Since the hydrophobic effect is involved in all ligand binding it seems quite hopeless to get any reliable numbers when neglecting entropy. No referee will buy that - I wouldn't. What do you think? -- On Oct 21, 2010, at 09:25 , Sander Pronk wrote: Hi Mohsen, The mean energy difference is only one component of the free energy difference. Before you go any further I'd suggest reading a good book on molecular simulations, like 'Understanding Molecular Simulations' by Frenkel and Smit. There's a good reason free energy calculations cover over half of that book. Sander On Oct 21, 2010, at 09:18 , mohsen ramezanpour wrote: Dear Justin If I do two MD simulations for a short time in the same conditions(of course separately for protein and drug) and calculate total energy of each one and sum them with each other as E1 as nonbonding free energy of system. then a MD simulation for Protein-drug system in the same condition and calculate it's total energy too as E2 as bound system . what does (E1-E2)mean? I think it is binding free energy,Is not it? in the other hand when we are working on NPT ensamble it means Gibbs free energy is the main energy and our total energy is equal to Gibbs free energy. Then,what is the problem? -- David van der Spoel, Ph.D., Professor of Biology Dept. of Cell & Molec. Biol., Uppsala University. Box 596, 75124 Uppsala, Sweden. Phone: +46184714205. sp...@xray.bmc.uu.sehttp://folding.bmc.uu.se -- gmx-users mailing listgmx-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
[gmx-users] RE: Gibbs free energy of binding
Actually, I believe that using the energy difference, Delta E, as an approximation to the free energy difference, Delta G, is a valid approach (which I'm considering myself). The entropic contribution to Delta G, namely -T Delta S, may be less prominent than Delta E. In addition, Delta S can be approximated by various means - see e.g. Doig & Sternberg 1995. I understand that such an approach is utilized in the Accelrys Discovery Studio. Obviously, this is an approximation that might be too crude for some applications. What do you think? -- On Oct 21, 2010, at 09:25 , Sander Pronk wrote: Hi Mohsen, The mean energy difference is only one component of the free energy difference. Before you go any further I'd suggest reading a good book on molecular simulations, like 'Understanding Molecular Simulations' by Frenkel and Smit. There's a good reason free energy calculations cover over half of that book. Sander On Oct 21, 2010, at 09:18 , mohsen ramezanpour wrote: > Dear Justin > > If I do two MD simulations for a short time in the same conditions(of course separately for protein and drug) > and calculate total energy of each one and sum them with each other as E1 as nonbonding free energy of system. > then a MD simulation for Protein-drug system in the same condition and calculate it's total energy too as E2 as bound system . > what does (E1-E2)mean? > I think it is binding free energy,Is not it? > in the other hand when we are working on NPT ensamble it means Gibbs free energy is the main energy and our total energy is equal to Gibbs free energy. > Then,what is the problem? -- gmx-users mailing listgmx-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
