Modeling of Human Neuraminidase-1 and Its Validation by LERE-Correlation Analysis

Abstract

Four human neuraminidases (hNEUs1-4) have been identified. Among them, hNEU1 has been studied extensively as a target for sialidosis. It has been desired to understand the biological functions of hNEU1 at the molecular and atomic levels. The three-dimensional structure of hNEU1 is not known at present. In the present work, we constructed a three-dimensional structure of hNEU1 by homology modeling, and then performed correlation analyses between observed and calculated free-energy changes (quantitative structure−activity relationship (QSAR) analyses), coupled with LERE (linear expression by representative energy terms) procedure using the modeled three-dimensional structure in order to confirm the validity of the modeled structure. The atomic coordinates of all atoms in the verified model of hNEU1 are available. The proposed structure of hNEU1 will be useful and helpful for further studies concerning the biological and chemical functions of hNEU1. The present article is one of continuous works derived from the one that won the CBI Award for the best presentation in the CBI/JSBi 2011 Joint Conference (presented by Seiji Hitaoka).