Computational Insights into ADAMTS4, ADAMTS5 and MMP13 Inhibitor Selectivity.

Published on Jul 1, 2012in Molecular Informatics2.741
· DOI :10.1002/MINF.201100131
Federico Filomia2
Estimated H-index: 2
(University of Modena and Reggio Emilia),
Puneet Saxena9
Estimated H-index: 9
(University of Modena and Reggio Emilia)
+ 3 AuthorsMaria Cristina Menziani28
Estimated H-index: 28
(University of Modena and Reggio Emilia)
The results obtained by means of Molecular Dynamics simulations and Multiway Explorative Data Analysis on ADAMTS4, ADAMTS5 and MMP13 complexed with Marimastat and two cis-1(S)2(R)-amino-2-indanol ligands suggest that determinant characteristics for ligand binding and selectivity among the three enzymes are to be found in the different protein conformation flexibility. Moreover, the role of the TS-domain in the inhibitor binding to ADAMTS enzymes has been investigated for the first time in this work. The results obtained suggest that the influence of the TS-domain on the S1′ loop fluctuations of ADAMTS4 and ADAMTS5 could be exploited for the design of therapeutics for chronic osteoarthritis diseases.
#1Jacob D. Durrant (UCSD: University of California, San Diego)H-Index: 22
#2J. Andrew McCammon (UCSD: University of California, San Diego)H-Index: 116
This review discusses the many roles atomistic computer simulations of macromolecular (for example, protein) receptors and their associated small-molecule ligands can play in drug discovery, including the identification of cryptic or allosteric binding sites, the enhancement of traditional virtual-screening methodologies, and the direct prediction of small-molecule binding energies. The limitations of current simulation methodologies, including the high computational costs and approximations of ...
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