Work

Farnesyl Diphosphate Synthase Inhibitors fromIn SilicoScreening

Year: 2013

Type: article

Abstract: The relaxed complex scheme is an in silico drug screening method that accounts for receptor flexibility using molecular dynamics simulations. Here, we used this approach combined with similarity searches and experimental inhibition assays to identify several low micromolar, non-bisphosphonate inhibitors, bisamidines, of farnesyl diphosphate synthase (FPPS), an enzyme targeted by some anticancer and antimicrobial agents and for the treatment of bone resorption diseases. This novel class of farnesyl diphosphate synthase inhibitors have more drug-like properties than existing bisphosphonate inhibitors, making them interesting pharmaceutical leads.

Source: Chemical Biology & Drug Design

DOI: 10.1111/cbdd.12121

Authors: Steffen Lindert, Wei Zhu, Yi‐Liang Liu, Ran Pang, Eric Oldfield, J. Andrew McCammon

Institutions: U.S. National Science Foundation, University of California San Diego, University of Illinois Urbana-Champaign, Howard Hughes Medical Institute

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Howard Hughes Medical Institute, National Cancer Institute, National Institute of General Medical Sciences, National Center for Research Resources