From chemistry-request@server.ccl.net Wed Dec 9 03:20:21 1998 Received: from www.ccl.net (www.ccl.net [192.148.249.5]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id DAA04599 for ; Wed, 9 Dec 1998 03:20:21 -0500 Received: from yxora.total.com (yxora.total.com [146.249.254.77]) by www.ccl.net (8.8.3/8.8.6/OSC/CCL 1.0) with SMTP id DAA06526 Wed, 9 Dec 1998 03:14:50 -0500 (EST) From: FRANCOIS.HUTSCHKA@total.com Received: by yxora.total.com; id JAA29815; Wed, 9 Dec 1998 09:14:10 +0100 Received: from av.total.com(146.249.253.65) by yxora.total.com via smap (3.2) id xma028890; Wed, 9 Dec 98 09:13:11 +0100 Received: from mailgate.total.com by av.total.com (SMI-8.6/SMI-SVR4) id JAA02836; Wed, 9 Dec 1998 09:13:10 +0100 Received: (from x400@localhost) by mailgate.total.com (8.6.8/8.6.6) id JAA10738 for chemistry@www.ccl.net; Wed, 9 Dec 1998 09:04:12 +0100 X400-Received: by /PRMD=TOTAL/ADMD=ATLAS/C=FR; Relayed; 09 Dec 1998 09:04:18 +0200 Date: 09 Dec 1998 09:04:18 +0200 Delivery-Date: 09 Dec 1998 09:04:12 +0100 Message-Type: Multiple Part X400-Originator: FRANCOIS.HUTSCHKA@total.com X400-MTS-Identifier: [/PRMD=TOTAL/ADMD=ATLAS/C=FR;PC-981209070418-6BBC] X400-Recipients: chemistry@www.ccl.net Original-Encoded-Information-Types: Teletex X400-Content-Type: P2-1988 Message-ID: Importance: normal Subject: Hydrogenolysis of S-S bond Autoforwarded: FALSE To: chemistry@www.ccl.net (Non Receipt Notification Requested) CC: FRANCOIS.HUTSCHKA@total.com (Non Receipt Notification Requested) Priority: normal Conversion: Allowed Conversion-With-Loss: Allowed Alternate-Recipient: Allowed Content-Identifier: Hydrogenolysis o Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 8Bit Dear Members, I am looking for theoretical studies on hydrogenolysis of S-S bonds of sulfides. Does anybody know some references ?. Thanks a lot. François Hutschka TOTAL RAFFINAGE DISTRIBUTION CERT BP 27 76700 HARFLEUR Tél:(33).2.35.55.13.53 Fax:(33).2.35.55.12.99 Email: francois.hutschka@total.com From chemistry-request@server.ccl.net Wed Dec 9 10:16:52 1998 Received: from www.ccl.net (www.ccl.net [192.148.249.5]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id KAA04787 for ; Wed, 9 Dec 1998 10:16:52 -0500 Received: from ccl.net (atlantis.ccl.net [192.148.249.4]) by www.ccl.net (8.8.3/8.8.6/OSC/CCL 1.0) with ESMTP id KAA08059 Wed, 9 Dec 1998 10:11:21 -0500 (EST) Received: from mail1.its.rpi.edu (root@mail1.its.rpi.edu [128.113.100.7]) by ccl.net (8.8.6/8.8.6/OSC 1.1) with ESMTP id KAA20827 for ; Wed, 9 Dec 1998 10:11:20 -0500 (EST) Received: from curtp5 (curtp5.chem.rpi.edu [128.113.21.59]) by mail1.its.rpi.edu (8.8.8/8.8.6) with SMTP id KAA188506; Wed, 9 Dec 1998 10:12:18 -0500 Message-ID: <366E8FD7.6BC7@rpi.edu> Date: Wed, 09 Dec 1998 09:57:41 -0500 From: "Curt M. Breneman" Reply-To: brenec@rpi.edu Organization: RPI Department of Chemistry X-Mailer: Mozilla 3.02 (WinNT; I) MIME-Version: 1.0 To: help@gaussian.com CC: chemistry@ccl.net Subject: Transition State Searching using EF Mode Walking Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Mike, Dave and Doug (..etc) We're having an unusual problem here with transition state optimization of a medium-sized molecule using opt=(ts,ef). The geometry seems correct in terms of Z-matrix variables, and will go through an FOPT cycle in which the attacking species simply moves away from the reactant. When opt=ts is attempted, the "Wrong Number of Negative Eigenvalues" message comes up, but I'm not too surprised about that. Usually, we've had good luck with the EF mode-walking approach when other things fail. In this case, the EF mode-walking fails with a message that says: "Initef fails: Wrong number of Degrees of Freedom (Supposed to be 1-50 but 54 are found)". What's up here? Any advice would be appreciated. Curt Breneman RPI Chemistry From chemistry-request@server.ccl.net Wed Dec 9 10:44:18 1998 Received: from www.ccl.net (www.ccl.net [192.148.249.5]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id KAA04800 for ; Wed, 9 Dec 1998 10:44:18 -0500 Received: from mallard.duc.auburn.edu (mallard2.duc.auburn.edu [131.204.2.23]) by www.ccl.net (8.8.3/8.8.6/OSC/CCL 1.0) with ESMTP id KAA08278 Wed, 9 Dec 1998 10:38:46 -0500 (EST) Received: from localhost (youngd2@localhost) by mallard.duc.auburn.edu (8.8.8+Sun/8.8.8) with SMTP id JAA07117 for ; Wed, 9 Dec 1998 09:38:49 -0600 (CST) X-Authentication-Warning: mallard.duc.auburn.edu: youngd2 owned process doing -bs Date: Wed, 9 Dec 1998 09:38:49 -0600 (CST) From: David Young X-Sender: youngd2@mallard2 To: CHEMISTRY@www.ccl.net Subject: Chem Topic: QM/MM Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Content-Transfer-Encoding: 8bit X-MIME-Autoconverted: from QUOTED-PRINTABLE to 8bit by server.ccl.net id KAA04801 Hello all, I have written the following short essay for my users and am posting it here for your enjoyment and comments. I didn't find as many review articles as I wanted, so I would appreciate any references to QM/MM review literature. Thanks. My compilation of chemical topics can be accessed via the web at URL http://www.auburn.edu/~youngd2/topics/contents.html --------------------------------------------------------------------------- QM/MM David Young E-mail: dyoung@asc.edu Alabama Research & Education Network Nichols Research Corporation Division of University Computing 144 Parker Hall Auburn University Auburn, AL 36849 Various computational methods have strengths and weaknesses. Molecular mechanics can model very large compounds quickly. Quantum mechanics is able to compute many properties and model chemical reactions. It is possible to combine these two methods into one calculation, which models a very large compound using molecular mechanics and one crucial section of the molecule with quantum mechanics. This is designed to give results that have very good speed where only one region needs to be modeled quantum mechanically. This can also be used to model a molecule surrounded by solvent molecules. 1 Non-automated procedures The earliest combined calculations were done simply by modeling different parts of the system with different techniques. For example, some crucial part of the system could be modeled by using an ab initio geometry optimized calculation. The complete system could then be modeled using molecular mechanics, by holding the geometry of the initial region fixed and optimizing the rest of the molecule. This procedure gives a geometry for the whole system, although there is no energy expression that reflects non-bonded interactions between the regions. One use is to compute the conformational strain in ligands, which is important in determining the possibility of binding. In order to do this, the central portion is removed from the calculation, leaving just the ligands in the geometry from the complete system. Two energy calculations on these ligands are then performed, one without geometry optimization and one with geometry optimization. The difference between these two energies is the conformational strain that must be introduced into the ligands in order to form the compound. Another technique is to use an ab initio method to parameterize force field terms specific to a single system. For example, an ab initio method can be used to compute the reaction coordinate for a model system. An analytic function can then be fitted to this reaction coordinate. A molecular mechanics calculation can then be performed with this analytic function being used to describe the appropriate bonds, etc. 2 Partitioning of Energy Quantitative energy values are one of the most useful results from computational techniques. In order to have a reasonable energy expression when two calculations are combined, it is necessary to know not only the energy of the two regions, but also the energy of interaction between those regions. There have been a number of energy computation schemes proposed. Most of these schemes can be expressed generally as E = EQM + EQM/MM + Epol + Eboundary The first two terms are the energies of the individual computations. The EQM/MM term is the energy of interaction between these regions, assuming that both regions remain fixed. It may include Van der Waals terms, electrostatic interactions, or any term in the force field being used. Epol is the effect of either region changing as a result of the presence of the other region, such as electron density polarization or solvent reorganization. Eboundary is a way of representing the effect of the rest of the surroundings, such as the bulk solvent. The individual terms in EQM/MM, Epol, and Eboundary are discussed in more detail in the following section s. 2-1 Van der Waals Most of the methods proposed include a van der Waals term for describing non-bonded interactions between atoms in the two regions. This is usually represented by a 6-12 potential of the form 12 6 EVdW = A/r - B/r The parameters A and B are those from the force field being used. A few studies have incorporated a hydrogen bonding term also. 2-2 Charge The other term that is very widely used is a Coulombic charge interaction of the form ECoulomb = Qi Qj / rij The subscripts i and j denote two nuclei, one in the QM region and one in the MM region. The atomic charges for the MM atoms are obtained by any of the techniques commonly used in MM calculations. The atomic charges for the QM atoms can be obtained by a population analysis scheme. Alternatively, there might be a sum of interactions with the QM nuclear charges plus the interaction with the electron density, which is an integral over the electron density. 2-3 Describing bonds between regions If the QM and MM regions are separate molecules, having non-bonded interactions only might be sufficient. If the two regions are parts of the same molecule, it is necessary to describe the bond connecting the two sections. In most cases, this is done using the bonding terms in the MM method being used. This is usually done by keeping every bond, angle or torsion term that incorporates one atom from the QM region. Alternatively, a few studies have been done in which a separate orbital based calculation was used to describe each bond connecting the regions. 2-4 Polarization The energy terms above allow the shape of one region to affect the shape of the other and include the energy of interaction between regions. However, these non-bonded energy terms assume that the electron density in each region is held fixed. This can be a reasonable approximation for covalent systems. This is a poor approximation where the QM region is being stabilized by its environment, as is the case with polar solvent effects. Polarization is usually accounted for by computing the interaction between induced dipoles. The induced dipole is computed by multiplying the atomic polarizability by the electric field present at that nucleus. The electric field used is often only that due to the charges of the other region of the system. In a few calculations, the MM charges have been included in the orbital based calculation itself as the interaction with point charges. 2-5 Solvent reorientation Many of the methods define an energy function, then use that function for the geometry optimization. However, there are some methods that use a minimal coupling between techniques for the geometry optimization, then add additional energy corrections to the single point energy. In the latter case, some researchers have included a correction for the effect of the solvent molecules reorienting in response to the solute. This is not a widespread technique mostly because there is not a completely rigorous way to know how to correct for solvent reorientation. 2-6 Boundary terms It is sometimes desirable to include the effect of the rest of the system, outside of the QM and MM regions. One way to do this is using periodic boundary conditions, as is done in liquid state simulations. Some researchers have defined a potential, which is intended to reproduce the effect of the bulk solvent. This solvent potential may be defined just for this type of calculation, or it may be a continuum solvation model. For solids, a set of point charges, called a Madelung potential is often used. 3 Energy subtraction An alternative formulation of QM/MM is the energy subtraction method. In this method, calculations are done on various regions of the molecule with various levels of theory. Then the energies are added and subtracted, to give suitable corrections. This results in computing an energy for the correct number of atoms and bonds, analogous to an isodesmic strategy. Three such methods have been proposed by Morokuma and co-workers. The integrated MO + MM (IMOMM) method combines an orbital based technique with an MM technique. The integrated MO + MO method (IMOMO) integrates two different orbital based techniques. The "our own n-layered integrated MO and MM" method (ONIOM) allows for three or more different techniques to be used in successive layers. The acronym ONIOM is often used to refer to all three of these methods since it is a generalization of the technique. This technique can be used to model a complete system as a small model system and the complete system. The complete system would be computed using only the lower level of theory. The model system would be computed with both levels of theory. The energy for the complete system, combining both levels of theory, would then be E = Elow,complete + Ehigh,model - Elow,model Likewise a three layer system, could be broken into small, medium, and large regions, to be computed with low medium and high levels of theory (L, M, H respectively). The energy expression would then be E = EH,small + EM,medium - EM,small + EL,large - EL,medium This method has the advantage of not requiring a parameterized expression to describe the interaction of various regions. Any systematic errors in the way that the lower levels of theory describe the inner regions will be canceled out. The geometry of one region will affect geometry of the other, because this is not a systematic effect. Assuming transferability of parameters, this method avoids any over counting of the non-bonded interactions. The disadvantage is that the lower levels of theory must be able to describe all atoms in the inner regions of the molecule. The effect of one region of the molecule causing polarization of the electron density in the other region of the molecule is incorporated only to the extent that the lower levels of theory describe polarization. This method requires more CPU time than most of the others mentioned. However the extra should be minimal since it is due to lower level calculations on smaller sections of the system. 4 Self consistent method Bersuker and coworkers have proposed a technique where by the atoms on the boundary between regions are included in both calculations. In this procedure, optimizations are done with each method, using the boundary atom charge from the other method and this is repeated until the geometry is consistent between the levels of theory. They specify that the boundary atom cannot be part of a pi bridge between regions. 5 Truncation of the QM region Molecular mechanics methods are defined atom by atom. Thus having a carbon atom without all of its bonds does not have a large affect on other atoms in the system. In contrast, quantum mechanical calculations use a wave function that can incorporate second atom effects. An atom with a nonfilled valence will behave differently than with the valence filled. Because of this, one must consider the way in which the quantum mechanical portion of the calculation is truncated. A few of the earliest methods did truncated the atom on the dividing line between regions. Leaving this unfilled valence is reasonable only for a few of the very approximate semiempirical methods that were used at that time. A number of methods fill the valence of the interface atoms with an extra orbital, sometimes centered on the connecting MM atom. This results in filling out the valence while requiring a minimum amount of additional CPU time. The concern, which is difficult to address, is that this might still result in affecting the chemical behavior of the interface atom or even inducing a second atom affect. The other popular solution is to fill out the valence with atoms. Usually, H atoms are used, although pseudo-halide atoms have been used also. These pseudo-halide atoms are parameterized to mimic the behavior of the MM atom it is substituted for. These extra atoms are called "link atoms" or "junction dummy atoms". The link atoms are not included in the energy expression used to describe the interaction between the regions of the system. The use of link atoms is somewhat questionable, since they are often not subtracted from the final energy expression and may polarize the QM region incorrectly. 6 Region partitioning The choice of where to locate the boundary between regions of the system is important. A number of studies have shown that very poor end results will be obtained if this is chosen improperly. Any bonds, which are being formed or broken, must be entirel y in the QM region of the calculation. Also, any section changing hybridization should be entirely in the QM region. Furthermore, it is best to keep conjugated or aromatic sections of the system completely in one of the regions. Where second or third atom effects are expected to be important, those atoms should be in the same region of the calculation. 7 Optimization The more recently developed methods define an energy expression for the combined calculation, then use that expression to compute gradients for a geometry optimization. Some of the earlier methods would use a simpler level of theory for the geometry optimization, then add additional energy corrections to a final single point calculation. The current generation is considered to be the superior technique. 8 Incorporating QM terms in force fields Rather than doing several complete calculations with an additional interface, it is possible to incorporate orbital based terms in a molecular mechanics method. The first methods for doing this incorporated simple Huckel or PPP semiempirical models to help describe pi system conjugation and aromaticity. There are also techniques for incorporating crystal field theory or ligand field theory type descriptions of transition metals, which have proven to be difficult to model entirely with molecular mechanics. 9 Recommendations To date there have not been any large-scale comparisons of QM/MM models in which many different techniques were compared against each other and experimental results for a range of chemical systems. There does tend to be some preference towards the use of link atoms in order to insure the correct chemical behavior of the quantum mechanical region. Researchers are advised to consider the physical consequences of the effects which are included or excluded from various methods, as applied to their specific system. It is also prudent to verify results against experimental evidence where possible. Bibliography Introductory descriptions are in A. R. Leach "Molecular Modelling Principles and Applications" Longman, Essex (1996). K. P. Eurenius, D. C. Chatfield, B. R. Brooks, M. Hodoscek, Int. J. Quantum Chem. 60, 1189 (1996). J. Gao, Acc. Chem. Res. 29, 298 (1996). Reviews of QM/MM are J. Gao, "Reviews in Computational Chemistry Volume 7" K. B. Lipkowitz, D. B. Boyd, Eds., 119, VCH, New York (1992). A. Warshel, "Computer Modeling of Chemical Reactions in Enzymes and Solutions" Wiley, New York (1991). E. Clementi, "Computational Aspects for Large Chemical Systems" Springer, New York (1980). Papers describing methods that incorporate modified orbitals are J. Gao, P. Amara, C. Alhambra, J. J. Field, J. Phys. Chem. A 102, 4714 (1998). V. Théry, D. Rinaldi, J.-L. Rivail, B. Maigret, G. G. Ferency, J. Comput. Chem. 15, 269 (1994). A. Warshel, M. Levitt, J. Molec. Biol. 103, 227 (1976). Methods describing methods using link atoms are M. J. Field, P. A. Bash, M. Karplus, J. Comput. Chem. 11, 700 (1990). U. C. Singh, P. A. Kollman, J. Comput. Chem. 7, 718 (1986). Energy subtraction methods are described in M. Svensson, S. Humbel, R. D. J. Froese, T. Matsubara, S. Sieber, K. Morokuma, J. Phys. Chem. 100, 19357 (1996). S. Humbel, S. Sieber, K. Morokuma, J. Chem. Phys. 105, 1959 (1996). F. Maseras, K. Morokuma, J. Comput. Chem. 16, 1170 (1995). The self consistent method is I. B. Bersuker, M. K. Leong, J. E. Boggs, R. S. Pearlman, Int. J. Quantum Chem. 63, 1051 (1997). Methods incorporating orbital based terms in molecular mechanics force fields are described in P. Comba, T. W. Hambley, "Molecular Modeling of Inorganic Compounds" VCH, New York (1995). V. J. Burton, R. J. Deeth, J. Chem. Soc., Chem. Commun. 573 (1995). P. Comba, M. Zimmer, Inorg. Chem. 33, 5368 (1994). N. L. Allinger, J. T. Sprague, J. Am. Chem. Soc. 95, 3893 (1973). From chemistry-request@server.ccl.net Wed Dec 9 23:07:38 1998 Received: from www.ccl.net (www.ccl.net [192.148.249.5]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id XAA05611 for ; Wed, 9 Dec 1998 23:07:33 -0500 Received: from mailer.scri.fsu.edu (mailer.scri.fsu.edu [144.174.112.142]) by www.ccl.net (8.8.3/8.8.6/OSC/CCL 1.0) with ESMTP id XAA09632 Wed, 9 Dec 1998 23:01:54 -0500 (EST) Received: from dirac.scri.fsu.edu (margit.scri.fsu.edu [144.174.128.45]) by mailer.scri.fsu.edu (8.8.7/8.7.5) with SMTP id XAA15204 for ; Wed, 9 Dec 1998 23:01:57 -0500 (EST) From: Michael Schimeczek Received: by dirac.scri.fsu.edu (5.67b) id AA32539; Wed, 9 Dec 1998 23:01:56 -0500 Message-Id: <199812100401.AA32539@dirac.scri.fsu.edu> Subject: Postdoc position To: CHEMISTRY@www.ccl.net Date: Wed, 9 Dec 1998 23:01:56 -0500 (EST) X-Mailer: ELM [version 2.4 PL24 ME8] Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit Dear CCLers, the following is from a friend of mine who is looking for a postdoc. Please forward this to whoever might be interested. Thank you! Michael --------------------------------------------- Dr. Michael Schimeczek Supercomputer Computations Research Institute 496 Dirac Science Library Florida State University Tallahassee, Florida 32306-4130, USA phone: (850) 644-7060 fax: (850) 644-0098 email: schimec@scri.fsu.edu --------------------------------------------- ----- Forwarded message from Hagai Meirovitch ----- ************************************************************* * * * POSTDOCTORAL POSITION IN COMPUTATIONAL STRUCTURAL BIOLOGY * * * ************************************************************* A postdoctoral position in Computational Structural Biology is available in the Supercomputer Computational Research Institute (SCRI) at Florida State University, Tallahassee, Florida. The candidate will take part in developing a theoretical methodology for analyzing data of flexible peptides and loops in proteins obtained by multidimensional NMR and X-ray crystallography. The project involves development of conformational search techniques, methods for calculating the free energy, and continuum solvation models. Monte Carlo and molecular dynamics simulations will be heavily used. The new computational tools will also be applied to problems in homology and threading. Experience with the above topics is desirable, and familiarity with software packages such as AMBER or GROMOS is an advantage. Please send resume by mail, e-mail or fax, and two letters of recommendation to Dr. Hagai Meirovitch, SCRI, Florida State University, Tallahassee, Fl 32306-4130. Fax: 850-644-0098, E-mail: hagai@scri.fsu.edu ----- End of forwarded message from Hagai Meirovitch -----