Search for Improved Host Architectures: Application of de Novo Structure-Based Design and High-Throughput Screening Methods To Identify Optimal Building Blocks for Multidentate Ethers

J. Am. Chem. Soc., 127 (48), 17043 -17053, 2005. 10.1021/ja055169x S0002-7863(05)05169-3
Web Release Date: November 2, 2005

Search for Improved Host Architectures: Application of de Novo Structure-Based Design and High-Throughput Screening Methods To Identify Optimal Building Blocks for Multidentate Ethers

Benjamin P. Hay,* Alexander A. Oliferenko, Jamal Uddin, Cungen Zhang, and Timothy K. Firman

Contribution from the Chemical Sciences Division, Pacific Northwest National Laboratory, PO Box 999, Richland, Washington 99352

ben.hay@pnl.gov

Received July 29, 2005

Abstract:

This paper presents a computational approach to the deliberate design of improved host architectures. The approach, which involves the use of computer-aided design software, is illustrated by application to cation hosts containing multiple aliphatic ether oxygen binding sites. De novo molecule building software, HostDesigner, is interfaced with molecular mechanics software, GMMX, providing a tool for generating and screening millions of potential bidentate building block structures. Enhanced cation binding affinity can be achieved when highly organized building blocks are used to construct macrocyclic hosts.

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