ABSTRACT
CONTENTS 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 5.2 Conformational Change of AdKArising from NMA .. . . . . . . . . . . . . . . . . . 93
5.2.1 Standard Normal Mode Calculation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 5.2.2 Comparison with the Conformational Change. . . . . . . . . . . . . . . . . . 94 5.2.3 Effective Number of Modes Required for the Description . . . . 95 5.2.4 RTB Approximation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 5.2.5 Tirion’s Approach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 5.2.6 Description of the Conformational Change with
Approximate Modes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 5.3 Conformational Change of DHFR and NMA .. . . . . . . . . . . . . . . . . . . . . . . . . 103 5.4 Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 5.5 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
The idea that protein functionalmotions canbewell describedwith a fewslow normal modes only, probably originates from the seminal study of hen-egg lysozyme hinge-bendingmotion, byMartin Karplus and coworkers, 30 years ago [1]. Indeed, after the calculation of an adiabatic potential for the anglebending, found to be approximately parabolic, these authors treated the relative motion of the two structural domains as an angular harmonic oscillator composed of two rigid spheres with moments of inertia corresponding to those of the domains. A vibrational frequency of 4.3 cm−1 was obtained, quite close to the lowest-frequency value found afterward, when standard normal mode analysis (NMA) was performed [2,3].
