From p.grootenhuis@organon.akzonobel.nl Tue Mar 12 04:21:15 1996 Received: from gatekeeper.oss.akzonobel.nl for p.grootenhuis@organon.akzonobel.nl by www.ccl.net (8.7.1/950822.1) id DAA22328; Tue, 12 Mar 1996 03:30:03 -0500 (EST) Received: (from mail@localhost) by gatekeeper.oss.akzonobel.nl (8.6.12/8.6.12) id JAA03370 for ; Tue, 12 Mar 1996 09:33:15 +0100 Received: from apou01.akzonobel.nl(145.49.90.59) by gatekeeper.oss.akzonobel.nl via smap (V1.3) id sma032068; Tue Mar 12 09:32:56 1996 Received: by apou01.akzonobel.nl (8.7.1/AKZONOBEL-WvdL/951013) id JAA05463; Tue, 12 Mar 1996 09:28:07 GMT Received: (from groot@localhost) by organon.akzonobel.nl (950511.SGI.8.6.12.PATCH526/8.6.12) id JAA08196 for chemistry@www.ccl.net; Tue, 12 Mar 1996 09:29:47 GMT From: Peter Grootenhuis Message-Id: <199603120929.JAA08196@organon.akzonobel.nl> Subject: MD of non-globular proteins - answers To: chemistry@www.ccl.net Date: Tue, 12 Mar 1996 09:29:44 +0000 (WET) Name: P.Grootenhuis Organisation: NV Organon Phone: (+31)0412-661920 X-Mailer: ELM [version 2.4 PL24 ME8b] MIME-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit CCL-ers, My original questions concerned MD of non-globular proteins where I observed both in gas-phase and aqueous simulations a rather strong tendency of the system to adopt conformations that result in more globular shapes. Questions: (1) Is anybody aware of (published) MD simulations of non-globular proteins ? (2) Does anybody has (preferably computationally inexpensive) suggestions on how to handle such a system ? Thanks for your suggestions! Here is a summary: ------------------------------------------------------------------------------- From: bear@ellington.pharm.arizona.edu (Soaring Bear) Sounds like you ought to use more gentle methods, like lower temp, ramp gradient, shorter times, higher dielectric. ------------------------------------------------------------------------------- From: Willy Wriggers The problems you mentioned have also been observed by us. We carry out MD simulations of calmodulin, a dumbbell shaped protein of only 148 aa residues, in solution (see "calmodulin" on my homepage at http://www.ks.uiuc.edu/~wriggers/). Earlier simulations by our collaborators at CUNY (see Pascal-Ahuir, Mehler, Weinstein: Molecular Engineering 1, 231-247, 1991 for review) had a limited solvent model (only explicit surface waters) and it could not be ruled out that observed structural changes were caused by the protein "sticking it's tongue out" of the water molecules, which tend to diffuse to the center of the protein. The way we solve the problem now is by placing the protein in a 44 A radius sphere of water, which brings the total system size to 33,000 atoms. Since the explicit solvent model and salt ions slow down the movement of calmodulin's domains, we need to simulate for 3 ns. I know such a calculation may not be feasible in every case. If you have limited resources, it's better to simulate only parts of the protein which are of interest, i.e. use stochastic boundary conditions (Brooks, Karplus, Pettitt: Proteins. (1988) Wiley Interscience Pub.). I would not recommend using a distance-dependent dielectric constant to model the solvent because it gives you the wrong electrostatics. Depending on your problem, you may also want to look at other newer "in vacuo" simulation techniques which use constraints (Collins, Burt, Erickson: Flap opening in HIV-1 protease... (1995) Nature Struct. Biol. 2:334-338). ------------------------------------------------------------------------------- From: alper@netcom.com (Howard Alper) In your simulations, how do you treat the nonbonded interactions. In particular, do you use switching functions? The reason I ask is that while these functions do smooth away discontinuities in the energy, they can create artificial maxima and minima in the interatomic, interresidue, or intermolecular forces that could trap the particles at particular separations from each other. This can be seen by looking at the way the switching function varies in the region where it goes from 1 to 0, and considering what the derivative of the function would look like. I have seen this for simulations of neat water (K. Lau. H. E. Alper, T. Thacher, and T. R. Stouch, J. Phys. Chem. 98, 8785 (1994)), as well as in simulations of lipid bilayer systems. Switching functions can decrease the degree of motion a system undergoes, compared to other cutoff methods... ------------------------------------------------------------------------------- From: Vincent Collura I am not surprised about " a tendency" to fold into a globular (more compact) shape in the gas-phase, the reason is certainly the electrostatics term of the nonbonded energy. The best is to increase the dielectric constant (distance dependent or not in your case?) close to the value of water. In your case, it will be a good approximation because if it is not globular or compact it can be deduced that it has certainly a substantial part of the surface in contact with the solvent unless it is a membrane protein. I am slightly more surprised that you observed this effect with the explicit description of the solvent. Normally it should be more "rigid". If it is not a compact protein ( higher % of hydrophilic residues? Is there a well defined hydrophobic core in your protein ?) it is normal that it undergoes larger average fluctuation at room temperature in the solvent, but it should'nt lead to a more compact protein. Are you using Periodic Box conditions or only a water shell around the protein ? Have a look in the way the electrostatics terms are parameterized in your force field.... ______________________________________________________________________________ Dr. Peter D.J. Grootenhuis | N.V. Organon / CMC Dept. RK2337 | Phone : +31-412-661920 P.O. Box 20 / 5340 BH Oss | Fax : +31-412-662539 The Netherlands | E-mail : p.grootenhuis@organon.akzonobel.nl _________________________________|____________________________________________ From polowin@hyper.com Tue Mar 12 10:22:53 1996 Received: from www.hyper.com for polowin@hyper.com by www.ccl.net (8.7.1/950822.1) id KAA27797; Tue, 12 Mar 1996 10:02:13 -0500 (EST) Received: from joel (joel.hyper.com [204.50.97.14]) by www.hyper.com (8.6.12/8.6.12) with SMTP id KAA00401; Tue, 12 Mar 1996 10:17:01 -0500 Message-Id: <199603121517.KAA00401@www.hyper.com> Date: Tue, 12 Mar 96 09:57:59 -0500 From: Joel Polowin Organization: Hypercube, Inc. X-Mailer: Mozilla 1.1N (Windows; I; 16bit) MIME-Version: 1.0 To: chemistry@www.ccl.net, quant@cc.acad.md Subject: Re: ccl: C60 multiple moments Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=us-ascii > From: quant@cc.acad.md > Date: Tue, 27 Feb 96 14:41:55 -0200 > I tried to calculate the electronic structure of this > molecule with my own CNDO program using the example from the > HyperChem. These calculations give the non zero dipole moment > for C60. Another hand on a symmetry considerations the first > non zero moment of the molecule must be of 6th order. So my > questions are: > 1. Why the dipole moment obtained with both in my CNDO > version and HyperChem CNDO for C60 is non zero? > 2. Does anybody knows any calculations of electrical moments > for C60? When I optimize C60 with CNDO with HyperChem and calculate its dipole moment, I get the expected 0 dipole. I do not know why your result differs, but it seems to me that the most likely cause is that your structure is not optimized and not symmetrical. Joel ------------ Joel Polowin, Ph.D. Manager, Scientific Support Email to: polowin@hyper.com Hypercube Inc, 419 Phillip St, Waterloo, Ont, Canada N2L 3X2 (519)725-4040 Info requests to: info@hyper.com Support questions to: support@hyper.com Email group: Send "subscribe hyperchem" to hyperchem-request@hyper.com WWW: http://www.hyper.com/ From gl@coil.mdy.univie.ac.at Tue Mar 12 13:16:04 1996 Received: from coil.mdy.univie.ac.at for gl@coil.mdy.univie.ac.at by www.ccl.net (8.7.1/950822.1) id MAA29817; Tue, 12 Mar 1996 12:54:18 -0500 (EST) Received: by coil.mdy.univie.ac.at (940816.SGI.8.6.9/930416.SGI.AUTO) for chemistry@www.ccl.net id SAA21268; Tue, 12 Mar 1996 18:52:14 +0100 From: "Gerald Loeffler" Message-Id: <9603121852.ZM21266@coil.mdy.univie.ac.at> Date: Tue, 12 Mar 1996 18:52:13 +0100 X-Mailer: Z-Mail (3.2.0 26oct94 MediaMail) To: chemistry@www.ccl.net Subject: OFF Files and MD Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Hi! In the manual for LEAP, a program used to setup systems for MD calculations that came with our AMBER-distribution from Oxford Molecular, I read about OFF (Object File Format). It says there: OFF is a general file format developed for LEAP... It is intention that future versions of AMBER and SPASMS will read this OFF file, rather than topology and coordinate files, for input data to molecular mechanics calculations. So OFF should contain all the information about a chemical system that is needed to start a MD simulation of that system: connectivities (topology), force-field parameters, positions and velocities of the atoms - but not the characteristics of the MD-simulation itself (as I understand it!). Before I start worrying about OFF at all, I would really like to know: 1) When will there actually be a MD-program that understands OFF? 2) Will OFF only be supported by AMBER (and SPASMS) or is there a chance that other MD-programs (CHARMM, discover) will read OFF. 3) Is there a (definitive) specification of OFF somewhere. 4) Is there any other movement towards a universal file-format for the specification of chemical systems for MD-simulations? Thanks a lot for your attention! -gerald -- Gerald Loeffler PhD student in Theoretical Biochemistry EMail: Gerald.Loeffler@mdy.univie.ac.at Phone: +43 1 40480 612 Fax: +43 1 4028525 SMail: University of Vienna Institute for Theoretical Chemistry Theoretical Biochemistry Group Waehringerstrasse 17/Parterre A-1090 Wien, Austria