Application of Computational Methods for the Design of BACE-1 Inhibitors: Validation of in Silico Modelling

被引：17

作者：

Bajda, Marek ^{[1
,2
]}

Jonczyk, Jakub ^{[2
]}

Malawska, Barbara ^{[2
]}

Filipek, Slawomir ^{[1
]}

机构：

[1] Univ Warsaw, Fac Chem, PL-02093 Warsaw, Poland

[2] Jagiellonian Univ, Dept Physicochem Drug Anal, Coll Med, Fac Pharm, PL-30688 Krakow, Poland

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2014年 / 15卷 / 03期

关键词：

-secretase; BACE-1; inhibitor; molecular modelling; docking studies; validation; ALZHEIMERS-DISEASE; BETA-SECRETASE; THERAPEUTIC TARGET; CELL BIOLOGY; PART; 2ND-GENERATION; IDENTIFICATION; DISCOVERY; DERIVATIVES; SITE;

D O I：

10.3390/ijms15035128

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

-Secretase (BACE-1) constitutes an important target for search of anti-Alzheimer's drugs. The first inhibitors of this enzyme were peptidic compounds with high molecular weight and low bioavailability. Therefore, the search for new efficient non-peptidic inhibitors has been undertaken by many scientific groups. We started our work from the development of in silico methodology for the design of novel BACE-1 ligands. It was validated on the basis of crystal structures of complexes with inhibitors, redocking, cross-docking and training/test sets of reference ligands. The presented procedure of assessment of the novel compounds as -secretase inhibitors could be widely used in the design process.

引用

页码：5128 / 5139

页数：12

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