Abstract：
:Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibition of the human Farnesyl Pyrophosphate Synthase (hFPPS). Available inhibitory activity values show that 2G-BPs act time-dependently, showing big differences in their initial inhibitory activities but similar final IC50 values. However, there is a lack of information explaining this similar final inhibitory potency. Although different residues have been identified in the stabilization of the R2 side chain of 2G-BPs into the active site, similar free binding energies were obtained that highlighted a similar stability of the ternary complexes, which in turns justified the similar IC50 values reported. Free binding energy calculations also demonstrated that the union of 2G-BPs to the active site were 38 to 54 kcal mol-1 energetically more favourable than the union of the natural substrate, which is the basis of the inhibition potency of the hFPPS activity.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Fernández D,Ramis R,Ortega-Castro J,Casasnovas R,Vilanova B,Frau Jdoi
10.1007/s10822-017-0034-5subject
Has Abstractpub_date
2017-07-01 00:00:00pages
675-688issue
7eissn
0920-654Xissn
1573-4951pii
10.1007/s10822-017-0034-5journal_volume
31pub_type
杂志文章abstract：:The one-dimensional model of Hann et al. (JChem Inf Comput Sci 41(3):856–864) has been extended to include reverse binding and wrap-around interaction modes between the protein and ligand to explore the complete combinatorial matrix of molecular recognition. The cumulative distribution function of the Maxwell–Boltzman...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-013-9683-1
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-011-9533-y
更新日期：2012-06-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1007963901092
更新日期：1997-09-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-004-7878-1
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-005-9020-4
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-015-9872-1
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journal_title：Journal of computer-aided molecular design
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doi：10.1023/b:jcam.0000046819.20241.16
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-012-9620-8
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/BF00129422
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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