Free Energy Estimation and Automated Docking of Carbohydrates to Proteins

Iowa State University, Ames IA

Investigators

Abstract

This project envisions work in two interrelated areas: 1) the extension and improvement of a partially completed computational method to estimate the free energies of binding of carbohydrate ligands to proteins, either enzymes or lectins; and 2) computational docking using AutoDock of many different carbohydrates substrates into glycoside hydrolase Families 1 (B-glucosidases, B-galactosidases, B-mannosidases, 6-phospho-B-galactosidases, 6-phospho-B-glucosidases, and myrosinases), 2 (B-galactosidases, B-glucuronidases, and B-mannosidases), 6 (cellobiohydrolases and endoglucanases), and 7 (cellobiohydrolases and endoglucanases). The impacts of this project are potentially the following: 1) A very useful computational model that until recently predicted general energies of binding of carbohydrates to proteins will be made much more precise, and will better predict actual binding free energies; 2) in a more general fashion, the importance of computational tools to supplement and extend experimental protein structural data will be further demonstrated; 3) the mechanisms of the enzymes in several very extensive and important glycosyl hydrolase families will be better elucidated, giving members of the communities researching these enzymes new insights not easily obtained by experimental studies; 4) a number of graduate and undergraduate students will be trained in the area of computational enzyme structure-function determination, where there is a paucity of well-trained practitioners and an overwhelming amount of raw and partially data to be processed and understood.