1tnh
From Proteopedia
(New page: 200px<br /><applet load="1tnh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tnh, resolution 1.8Å" /> '''PREDICTION OF NOVEL S...) |
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| - | [[Image:1tnh.jpg|left|200px]]<br /><applet load="1tnh" size=" | + | [[Image:1tnh.jpg|left|200px]]<br /><applet load="1tnh" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1tnh, resolution 1.8Å" /> | caption="1tnh, resolution 1.8Å" /> | ||
'''PREDICTION OF NOVEL SERINE PROTEASE INHIBITORS'''<br /> | '''PREDICTION OF NOVEL SERINE PROTEASE INHIBITORS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We describe here the use of a rapid computational method to predict the | + | We describe here the use of a rapid computational method to predict the relative binding strengths of a series of small-molecule ligands for the serine proteinase trypsin. Flexible molecular models of the ligands were docked to the proteinase using an all-atom potential set, without cutoff limits for the non-bonded and electrostatic energies. The binding-strength calculation is done directly in terms of a molecular mechanics potential. The binding of eighteen different compounds, including non-binding controls, has been successfully predicted. The measured Ki is correlated with the predicted energy. The correctness of the theoretical calculations is demonstrated with both kinetics measurements and X-ray structure determination of six enzyme-inhibitor complexes. |
==About this Structure== | ==About this Structure== | ||
| - | 1TNH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with CA and FBA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] Full crystallographic information is available from [http:// | + | 1TNH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=FBA:'>FBA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TNH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Trypsin]] | [[Category: Trypsin]] | ||
| - | [[Category: Harrison, R | + | [[Category: Harrison, R W.]] |
[[Category: Kurinov, I.]] | [[Category: Kurinov, I.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: hydrolase(serine proteinase)]] | [[Category: hydrolase(serine proteinase)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:15:26 2008'' |
Revision as of 13:15, 21 February 2008
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PREDICTION OF NOVEL SERINE PROTEASE INHIBITORS
Overview
We describe here the use of a rapid computational method to predict the relative binding strengths of a series of small-molecule ligands for the serine proteinase trypsin. Flexible molecular models of the ligands were docked to the proteinase using an all-atom potential set, without cutoff limits for the non-bonded and electrostatic energies. The binding-strength calculation is done directly in terms of a molecular mechanics potential. The binding of eighteen different compounds, including non-binding controls, has been successfully predicted. The measured Ki is correlated with the predicted energy. The correctness of the theoretical calculations is demonstrated with both kinetics measurements and X-ray structure determination of six enzyme-inhibitor complexes.
About this Structure
1TNH is a Single protein structure of sequence from Bos taurus with and as ligands. Active as Trypsin, with EC number 3.4.21.4 Full crystallographic information is available from OCA.
Reference
Prediction of new serine proteinase inhibitors., Kurinov IV, Harrison RW, Nat Struct Biol. 1994 Oct;1(10):735-43. PMID:7634078
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