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Science 30 January 1987:
Vol. 235. no. 4788, pp. 574 - 576
DOI: 10.1126/science.3810157
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Articles

Science, Vol 235, Issue 4788, 574-576
Copyright © 1987 by American Association for the Advancement of Science

articles

Calculation of the relative change in binding free energy of a protein-inhibitor complex

PA Bash, UC Singh, FK Brown, R Langridge, and PA Kollman

By means of a thermodynamic perturbation method implemented with molecular dynamics, the relative free energy of binding was calculated for the enzyme thermolysin complexed with a pair of phosphonamidate and phosphonate ester inhibitors. The calculated difference in free energy of binding was 4.21 +/- 0.54 kilocalories per mole. This compares well with the experimental value of 4.1 kilocalories per mole. The method is general and can be used to determine a change or "mutation" in any system that can be suitably represented. It is likely to prove useful for protein and drug design.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Hidden thermodynamics of mutant proteins: a molecular dynamics analysis.
J Gao, K Kuczera, B Tidor, and M Karplus (1989)
Science 244, 1069-1072
   Abstract »    PDF »
Computer-aided molecular design.
J. McCammon (1987)
Science 238, 486-491
   Abstract »    PDF »
Free energy calculations by computer simulation.
P. Bash, U. Singh, R Langridge, and P. Kollman (1987)
Science 236, 564-568
   Abstract »    PDF »
Evaluation of intrinsic binding energy from a hydrogen bonding group in an enzyme inhibitor.
P. Bartlett and C. Marlowe (1987)
Science 235, 569-571
   Abstract »    PDF »
Structures of two thermolysin-inhibitor complexes that differ by a single hydrogen bond.
D. Tronrud, H. Holden, and B. Matthews (1987)
Science 235, 571-574
   Abstract »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)