Computational Studies of Molecular Recognition, Biological Catalysis and Ion Channels
Title: Computational Studies of Molecular Recognition, Biological Catalysis and Ion Channels
SNIC Project: SNIC 007/07-47
Project Type: SNAC Large
Principal Investigator: Johan Åqvist <>
Duration: 2007-07-01 – 2008-01-31
Classification: 151701 151101 164102
Keywords: structure-based ligand design, biological catalysis, ribosome, ion channels, computer simulation


This proposal deals with computational studies in three fields of structural biochemistry: (1) structure-based ligand design and molecular recognition (2) biological catalysis and (3) K+ channel blocking. Particularly in the first of these areas, methodological development constitutes an important part of our planned work. Our main objectives are as follows. We will seek to further develop techniques for quantitative analysis and prediction of receptor-ligand binding affinities with emphasis on structure-based drug design. Several new promising lines of development are currently being pursued. In the second area, we will put a major effort into computational modelling of different steps involved in protein synthesis on the ribosome. The overall goal here is to bridge the gap between ribosome structure and function by exploring the energetics of different interactions and processes. With regard to enzyme catalysis we also intend to investigate the structural basis of temperature adaptation in enzymes from cold- and warm-active species, where we are currently focusing on citrate synthases from three different species. Furthermore, we will explore the structural and energetic binding characteristics of K+ channel blockers and derive models of the pore forming parts of some human K+ channels of pharmaceutical relevance. Very encouraging results have already been obtained for two of the most pharmaceutically interesting cardiac channels.