From owner-chemistry@ccl.net Wed Feb 8 01:18:00 2017 From: "Michael K. Gilson mgilson%ucsd.edu" To: CCL Subject: CCL: Entropy of a Bimolecular System Message-Id: <-52633-170208011736-25677-gtYBfeAh4j+smf5V3tl4zQ^server.ccl.net> X-Original-From: "Michael K. Gilson" Content-Transfer-Encoding: 8bit Content-Type: text/plain; charset=utf-8; format=flowed Date: Tue, 7 Feb 2017 22:17:28 -0800 MIME-Version: 1.0 Sent to CCL by: "Michael K. Gilson" [mgilson]![ucsd.edu] Yes, the RRHO approximation should be applied to the complex and then separately to each of the two free molecules. Regards, Mike On 2/7/2017 1:22 PM, Eric Hermes erichermes^-^gmail.com wrote: > Sent to CCL by: Eric Hermes [erichermes[#]gmail.com] > EC, > > You are on the right path. First, it is important to understand how > free energies of gas-phase species are calculated. I would suggest > reading the relevant chapters of McQuarrie's Statistical Mechanics (5 > through 8 in my version) or Hill's Introduction to Statistical > Thermodynamics (5 through 9). > > The free energy of a gas-phase molecule has contributions from the > electronic degrees of freedom, translation, rotation, and vibration. > > Typically, the free energy from electronic degrees of freedom is > assumed to be the potential energy plus an entropic term arising from > multiplicity. This comes from the assumption that excited electronic > states are thermally inaccessible, but this assumption breaks down if > the system has low-lying excited states or is metallic. > > The translational free energy is typically calculated using the > particle-in-a-box picture and employing the ideal gas approximation. In > your case, this is where the confusion arises. If you treat the > bimolecular system as a single system with only three degrees of > translational freedom, you are going to massively underestimate the > amount of entropy. Instead, you must consider them as two separate non- > interacting systems with three degrees of translational freedom each. > > The rotational free energy is typically calculated by employing the > rigid rotor approximation. If you treat your bimolecular system as a > single system, you will also be calculating this value incorrectly, as > a system composed of two non-bonded molecules is not a rigid rotor. > > The vibrational free energy is typically calculated by employing the > harmonic oscillator approximation. For this, the second derivative > matrix of the energy (the Hessian) is calculated and diagonalized. The > eigenvalues of the Hessian correspond to vibrational frequencies and > the eigenvectors the corresponding normal modes. The Hessian is 3N > dimensional, and since there are only 3N-6 vibrational modes (3N-5 if > the molecule is linear), the 6 lowest frequency modes are typically > discarded -- these should correspond to some linear combination of > translational and rotational modes. If you treat your bimolecular > system as a single system, you will likely have an additional 6 low > frequency modes corresponding to additional rotations or intermolecular > translations. > > In summary, make sure you are accounting for each species degrees of > freedom correctly: 1 electronic, 3 translational, 3 rotational (2 if > linear), and 3N-6 vibrational (3N-5 if linear) modes per molecule. > Also, remember that the resulting free energy is the free energy at the > standard state, typically 298 K and 1 atm. > > Eric > > On Tue, 2017-02-07 at 11:48 -0600, Ernest Chamot > echamota/chamotlabs.com wrote: >> Hi All, >> >> I seem to have argued myself into a state of confusion: I guess I >> just don’t really understand the entropy of a bimolecular system. >> >> I can calculate the enthalpy of a molecule with any number of >> methods, and so long as I also do an IR or frequency calculation, I >> can also get the entropy, and ultimately the free energy of the >> molecule. So if I am considering the equilibrium of a dissociation >> reaction, I can get the heat of reaction by modeling all three >> species, and subtracting the enthalpy of the reactant from the sum of >> the enthalpies of the products. But how do I calculate the free >> energy of reaction? >> >> I can’t just add up the individual free energies, can I? Isn’t the >> entropy of the pair of product molecules different from just the sum >> of the two individual entropies? Since there are two separate >> molecules in the same frame of reference, there should be an >> additional 6 degrees of freedom for the second molecule, even at >> infinite separation. Or do these all have a correspondence with a >> vibrational mode in the original reactant molecule? Doesn’t there >> need to be an additional term or factor: ln(2), or angular momentum, >> or something? >> >> (I’m interested in the overall reaction, not with the two product >> molecules still bound together in some intermediate complex. >> Otherwise I could just model that.) >> >> Thanks for any help. >> >> EC >> >> >> Ernest Chamot >> Chamot Labs, Inc. >> http://www.chamotlabs.com> > -- Michael K. Gilson, M.D., Ph.D. Professor, Skaggs School of Pharmacy and Pharmaceutical Sciences UC San Diego 9500 Gilman Drive La Jolla, CA 92093-0736 voice: 858-822-0622 http://gilson.ucsd.edu http://bindingdb.org http://drugdiscovery.ucsd.edu http://drugdesigndata.org From owner-chemistry@ccl.net Wed Feb 8 01:53:00 2017 From: "Norrby, Per-Ola Per-Ola.Norrby _ astrazeneca.com" To: CCL Subject: CCL: Entropy of a Bimolecular System Message-Id: <-52634-170208012945-29231-dcq7qtr4HNCDMTlX8iFxLA[a]server.ccl.net> X-Original-From: "Norrby, Per-Ola" Content-Language: en-US Content-Type: multipart/alternative; boundary="_000_HE1PR04MB2092D65430909DFD855D1709CA420HE1PR04MB2092eurp_" Date: Wed, 8 Feb 2017 06:29:33 +0000 MIME-Version: 1.0 Sent to CCL by: "Norrby, Per-Ola" [Per-Ola.Norrby!=!astrazeneca.com] --_000_HE1PR04MB2092D65430909DFD855D1709CA420HE1PR04MB2092eurp_ Content-Type: text/plain; charset="utf-8" Content-Transfer-Encoding: base64 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CjwvaHRtbD4NCg== --_000_HE1PR04MB2092D65430909DFD855D1709CA420HE1PR04MB2092eurp_-- From owner-chemistry@ccl.net Wed Feb 8 09:20:00 2017 From: "Josh Berryman josh.berryman(-)uni.lu" To: CCL Subject: CCL: Entropy of a Bimolecular System Message-Id: <-52635-170208055244-26595-LeOMdffsJN24JIFsOSCuww a server.ccl.net> X-Original-From: "Josh Berryman" Date: Wed, 8 Feb 2017 05:52:42 -0500 Sent to CCL by: "Josh Berryman" [josh.berryman*_*uni.lu] >>entropy of solvation. Frankly, thats beyond me, if youre interested in that, some expert will have to comment. I'll have a go then. I have a couple papers where I apply this stuff so I suppose that makes me an expert, although the people who write the codes I use certainly know more. Getting solvation entropy right is hard. The usual first approach is to use a continuum model of the solvent: Poisson-Boltzmann. [ wikipedia describes this reasonably well ]. This includes reaction field for burying charges and an estimated entropic cost for aligning the solvent dipoles to the solute field. It is a continuum theory so doesn't work well in situations where water structure is important (eg hydrogen bonds bridged by a localised water molecule, spine of hydration in DNA, etc etc). Salt is represented only by a change in the screening parameter, so if detailed interaction with salt is important (DNA again, etc etc) then PB will again give a quite wrong answer. By the standards of quantum codes PB is fast, however approximate versions (ALPBS, GBSA) are even faster, enough so as to be used in classical MD codes ("implicit solvent MD"). To go one better than PBSA you can use an integral-equation method to model continuous distributions of solvent atoms (atoms not molecules, so structure and orientation is preserved) around the solute, including 2-body ..N-body interaction terms. This type of approach is called 3D-RISM, there is at least as much to get your head around with this as there is with doing DFT on electrons. It is memory intensive and slow but yields *beautiful* plots of structure in the solvent around the solute. This brings up a point that is key to understand: entropy shouldn't be just a number. Its a description of the dynamical space of a system, and it is best consumed with a side- order of understanding about the shape of that space. Because of the volumetric information that it gives out, 3D-RISM is a really nice way to get some of that understanding. Another approach to step up from PBSA is to run some MD simulations of the solvent. There are different strategies to approach this: (1) You can phase from vacuum to explicit-solvent (eg TIP3P or SPC water) as a thermodynamic integration, and get the solvation free energy that way. (Maybe after a step of phasing from quantum to classical representation of your system). AMBER, Charmm etc wil allow these calculations as being fairly standard however they are not usually cheap as you need many integration points to get a good results. (2) You can MD in explicit water and try to estimate the solvation energy > from the behaviour of the solvent, eg via cell theory (Richard Henchman has some papers on this, its an approach which is in active development. There are a few strategies, Bill Goddard III has also got an approach for this, search Lin and Goddard). A simple and effective (but again, expensive) method is to histogram the visits of solvent molecules to different sub- volumes of the simulation system (Grid Inhomogenous Solvation Theory). Although its possible to have a lot of fun calculating solvation free energies, bear in mind that errors may cancel for you if you design your experiment nicely, so its possible to use a crude method like PBSA and still get the right free energy differences in the end. Josh Berryman Uni Luxembourg From owner-chemistry@ccl.net Wed Feb 8 09:55:00 2017 From: "Alessandra Magistrato alema:-:sissa.it" To: CCL Subject: CCL: CECAM Summer School on Atomistic Simulation Techniques in Trieste Message-Id: <-52636-170208065610-4529-c73jJOZr/4TplK6BT+iflQ#,#server.ccl.net> X-Original-From: "Alessandra Magistrato" Date: Wed, 8 Feb 2017 06:56:08 -0500 Sent to CCL by: "Alessandra Magistrato" [alema%sissa.it] Dear Collegues, we are pleased to announce the 7th edition of Summer School on Atomistic Simulation Techniques to be heald in Trieste, on 14-30 June 2017 The International School for Advanced Studies (SISSA) and CNR-IOM DEMOCRITOS Simulation Centre, Trieste (Italy), organize a CECAM Summer School on Atomistic Simulation Techniques, which this year will be dedicated to quantum mechanical methods and chemical and biochemical applications. The School is mainly directed to undergraduate and graduate students, with little or no experience in computer simulations. The purpose of the School will be threefold: (i) providing students with a basic but detailed overview of the theoretical foundations and numerical methods of quantum mechanical (QM) simulations of molecular and extended systems (ii) training them to solve quantum mechanical problems in practice, either implementing simple numerical codes from scratch or using existing QM codes for selected applications; (iii) giving an overview of the domains of current interesting research problems in material and biochemical science. At the end of the school the students should have a clear idea of the importance of quantum mechanical molecular simulations they should be aware of the problems that are still open and are at the center of current research efforts and should have the capability of developing their own simple code for performing a simulation or an analysis. For interested students with no previous experience in computational science it is possible to attend a three-day pre-school (14 - 16 June) devoted to the introduction to programming in C++/Fortran, with few numerical exercises. In 2017 the School will be entirely focused on quantum mechanics and in particular will be devoted to electronic properties of materials, chemical- and bio-molecules. The duration of the School is two weeks (plus the pre-school) To apply visit the School web site http://democritos.sissa.it/school2017/ and fill the application form http://www.democritos.it/school2017/appform.php Deadline for Applications The closing date for receipt of requests for participation is 31 March 2017 A registration fee (200 Euro) will be required to the accepted candidates and reimbursed to students who will have fully attended the school. The organizers will cover accommodation (14 nights), lunches and dinners at SISSA (Monday to Friday), public transportation and social dinner. Lodging expenses will be covered also during the pre-school. Limited support toward travel expenses can be provided in exceptional cases, based on fund availability. The organisers Stefano de Gironcoli (SISSA) Andrea Dal Corso (SISSA) Alessandra Magistrato (CNR-IOM %a% SISSA)