Summary of Research Project Results under JSPS FY2002
"Research for the Future Program"

1.Research Institution Okazaki National Research Institutes
2.Research Area Physical and Engineering Sciences
3.Research Field Computational Science and Engineering
4.Term of Project FY 1998 - FY 2002
5.Project Number 98P01101
6.Title of Project Development of Simulation Algorithms for the First-Principles Prediction of Three-Dimensional Structures of Proteins

7.Project Leader
Name Institution,Department Title of Position
Yuko, Okamoto Okazaki National Research Institutes, Institute for Molecular Science Associate Professor

8.Core Members

Name Institution,Department Title of Position
Fumio, Hirata Okazaki National Research Institutes, Institute for Molecular Science Professor
Mutsumi, Aoyagi Kyushu University, Computing and Communications Center Professor

9.Summary of Research Results

  The study of protein structures is directly related not only to drug design and de novo design of artificial proteins with specific functions but also the elucidation of the pathogenic mechanism for the disease that is caused by misfolding of proteins (such as mad cow disease and Alzheimer's disease). The goal of the present project is to develop an efficient simulation algorithm for the prediction of the three-dimensional structures of proteins from the first principles. In order to attain the goal, we have not only to have an efficient method for evaluation of solvation effects but also a powerful simulation algorithm that can avoid getting trapped in states of energy local minima. For the former, the RISM theory has been extensively improved. For the latter, we have developed more than 10 generalized-ensemble algorithms, among which it was found that the replica-exchange multicanonical algorithm, multicanonical replica-exchange method, replica-exchange simulated tempering, and multidimensional replica-exchange method are particularly powerful and suitable for protein structure predictions. By the development of these new methods, we conclude that we succeeded in attaining our goal. Now that the Human Genome Project has just completed the determination of the DNA base sequences that corresponds to the amino acid sequences of the proteins, the prediction of the three-dimensional structures of proteins will be one of the most important topics of research. The accomplishment of the present project will thus be very useful in the post-genome era not only in basic science but also in bioindustry.

10.Key Words
(1)protein   (2)molecular simulation   (3)molecular liquid theory
(4)electronic structure theory   (5)generalized-ensemble algorithm   (6)RISM
(7)multicanonical algorithm   (8)replica-exchange method   (9)post-genome