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From: Junmei Wang <junmwang.gmail.com>

Date: Tue, 24 Jun 2008 09:34:28 -0500

Hi, Floris,

Thank you very much for your input. Your result is very valuable for us to

develop better general AMBER force field. As you pointed out, the charges of

N (-1.0) and S (1.4) are too big and the electrostatic interaction is so

strong that the structure is distored when running minimization. When I used

larger dielectric constants or ran GB calculations, I got significantly

improved strcuctures. The following are structure parameters for IGB=5

minimization (500 steps), starting from the mopac minimized structure.

N-S 1.64 1.595

S-H 1.32 1.359

S-O 1.43 1.438, 1.438

N-H 1 1.018, 1.018

N-S-H 101.3 106.76

N-S-O 113.1 101.12, 101,17

H-N-S 108.3 101.65, 101.61

Best

Junmei

On Tue, Jun 17, 2008 at 4:57 AM, Floris Buelens <floris_buelens.yahoo.com>

wrote:

*> Dear AMBER users and developers,
*

*>
*

*> I'm interested in free energy calculations on ligand-protein complexes and
*

*> would like to thank the developers for their fantastic work on the AMBER and
*

*> GAFF force fields - I'm in the process of writing up some results for a
*

*> paper which will show very satisfactory agreement with experiment.
*

*> However I have come across an issue with GAFF parameters for sulfonamides,
*

*> for which I'd like to ask for your advice. From my test panel, I observed a
*

*> very significant systematic deviation in binding free energy for a subset of
*

*> sulfonamide-containing compounds. Inspection of MD trajectories shows what
*

*> look like unnatural angles of the H-N-S and N-S-O bonds, both of which are a
*

*> little over 90 degrees, as opposed to the ~110 published for HF/6-31+G*
*

*> calculations (Bharatam et al., Theoretical studies on S ± N interactions in
*

*> sulfonamides, Tetrahedron 58, 2002, 1759 - 1764).
*

*> I've attached a minimised structure of the sulfonamide used in the cited
*

*> study, and here's a quick comparison of the key bond lengths and angles
*

*> (left is Bharatam et al, right is minimised GAFF):
*

*>
*

*> N-S 1.64 1.55
*

*> S-H 1.32 1.36
*

*> S-O 1.43 1.42
*

*> N-H 1 1.01
*

*> N-S-H 101.3 108.47
*

*> N-S-O 113.1 94.38
*

*> H-N-S 108.3 94.39
*

*>
*

*> The most obvious discrepancies seems to be in the N-S-O and H-N-S angles
*

*> (18.7 and 13.9 degrees off), although difference the N-S bond length is also
*

*> significant. This is clearly due to the 1-4 interactions between the
*

*> strongly polarised N-bound hydrogens and S-bound oxygens.
*

*> I've done some initial testing of angles parameters to reproduce more
*

*> closely the H-N-S and N-S-O angles (I set equilibrium angles for both to 120
*

*> degrees and increased the H-N-S force constant by 50%), and this crude
*

*> approach appears to resolve something around half of my observed systematic
*

*> deviation.
*

*> I'd be very grateful if the GAFF developers could take some time to examine
*

*> the sulfonamide moeity more closely, or advise me how to generate parameters
*

*> which do not compromise the force field's consistency?
*

*> Many thanks for your time,
*

*>
*

*> Floris Buelens
*

*> Department of Crystallography, Birkbeck College, London
*

*>
*

*>
*

*> __________________________________________________________
*

*> Sent from Yahoo! Mail.
*

*> A Smarter Email http://uk.docs.yahoo.com/nowyoucan.html
*

*>
*

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Received on Wed Jun 25 2008 - 06:07:45 PDT

Date: Tue, 24 Jun 2008 09:34:28 -0500

Hi, Floris,

Thank you very much for your input. Your result is very valuable for us to

develop better general AMBER force field. As you pointed out, the charges of

N (-1.0) and S (1.4) are too big and the electrostatic interaction is so

strong that the structure is distored when running minimization. When I used

larger dielectric constants or ran GB calculations, I got significantly

improved strcuctures. The following are structure parameters for IGB=5

minimization (500 steps), starting from the mopac minimized structure.

N-S 1.64 1.595

S-H 1.32 1.359

S-O 1.43 1.438, 1.438

N-H 1 1.018, 1.018

N-S-H 101.3 106.76

N-S-O 113.1 101.12, 101,17

H-N-S 108.3 101.65, 101.61

Best

Junmei

On Tue, Jun 17, 2008 at 4:57 AM, Floris Buelens <floris_buelens.yahoo.com>

wrote:

-----------------------------------------------------------------------

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Received on Wed Jun 25 2008 - 06:07:45 PDT

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