Calculation of relative binding free energy difference of DHFR inhibitors by a Finite Difference Thermodynamic Integration (FDTI) approach

被引：7

作者：

Kamath, S ^{[1
]}

Coutinho, E ^{[1
]}

Desai, P ^{[1
]}

机构：

[1] Bombay Coll Pharm, Dept Pharmaceut Chem, Mumbai 400098, India

来源：

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS | 1999年 / 16卷 / 06期

关键词：

D O I：

10.1080/07391102.1999.10508331

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have implemented a Finite Difference Thermodynamic Integration (FDTI) approach to estimate the binding free energy relative to methotrexate (MTX) of three unreported inhibitors of DHFR. The validity of the calculation methodology was first proved by evaluating the relative binding free energy difference for two well-known anticancer agents aminopterin and methotrexate. The usefulness of the method in drug design has been demonstrated by the fact that inhibitor 5, designed by us was found to bind more tightly than MTX, by as much 7.5 kcal/mole and is a worthy candidate for further pharmacological investigations.

引用

页码：1239 / 1244

页数：6

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