Center for Molecular Spectroscopy and Dynamics

A. Ultimate Objectives

The ultimate objective of the CMDS is to develop a complete theoretical framework of coherent multidimensional spectroscopy for protein structure analysis, which includes determination of 3D conformation, investigation of protein folding pathway and mechanism, and elucidation of protein structure-function relationship. In order to achieve these goals, the three strategies summarized in the following Table 5 will be used.

Table 5. Research contents and strategies

The first step is to complete theoretical formulations of nonlinear vibrational and/or electronic response functions that correspond to ultrafast time-resolved coherent 2D and 3D spectroscopies. Once theoretical expressions of those response functions are obtained, using a variety of quantum chemistry calculation methods, molecular dynamics simulation, and computer programs developed by the CMDS over the last three years it will be possible to numerically calculate the 2D and 3D time-domain response functions. Subsequent 2D and 3D Fourier transformations will provide both time- and frequency-resolved multidimensional spectra that reveal a detailed dynamics and structure of the protein of interest. Then, numerous applications of coherent multidimensional spectroscopies to determination and investigation of protein structure, dynamics, and function will follow.

As will be emphasized in the follow section 4, the present research proposal is based on two hypotheses, (1) there is a one-to-one correspondence between the 3D protein structure and its multidimensional spectrum and (2) a time-resolved multidimensional spectrum obtained by utilizing ultrafast laser pulses can provide quantitative information on conformational fluctuation and transition, solvation dynamics stabilizing tertiary protein structure, and protein folding pathways, mechanism and function. Thus, an alternative way of defining the ultimate objective of the CMDS is to theoretically confirm these hypotheses.

B. Research objectives and scope by phase and by year

Research objectives by phase

<Phase One: Oct. 2000 ~ Sep. 2003>

· Theoretical investigation of the multidimensional vibrational and/or electronic response functions

· Numerical calculations of the multidimensional spectra of small molecules

As summarized in the CMDS Progress Report and Sec. 2 in the present proposal, we have accomplished the objectives of the first phase (for the first three years from Oct. 2000 to Sep. 2003) set up at the beginning of the Center for Multidimensional Spectroscopy (CMDS). We have completed two series of papers on both coherent 2D and 3D spectroscopies and recently proposed a few more novel coherent multidimensional spectroscopies which has not been experimentally confirmed their feasibility yet due to the limitations of current laser technology. Secondly, we have developed critical computational codes that can be used to numerically calculate coherent multidimensional spectra of small molecules, in combination with commercially available programs such as Gaussian, MOPAC, AMBER etc. Acetonitrile, N-methylacetamide (monopeptide), glycine dipeptide, tripeptides, and pentapeptides were under investigation by applying computation procedures developed by the CMDS and the principal rules and theoretical models have been thoroughly tested by making direct comparisons with experimental results. Since most of detailed discussions on the research results presented by the CMDS over the last three years were summarized in the Progress Report and in Sec.2, we shall not elaborate on them further in this section. Instead, hereafter we will describe detailed objectives and research subjects that will be studied during the Phase Two, from Oct. 2003 to Sep. 2006.

<Phase Two: Oct. 2003 ~ Sep. 2006>

· Calculations of the coherent multidimensional spectra and vibrational circular dichroic responses of small proteins with a few amino-acids as well as of natural proteins in their equilibrium and non-equilibrium states

In the second phase of the CMDS, a series of systematic calculations of coherent multidimensional spectra as well as vibrational circular dichroic responses of intermediate size polypeptides and relatively small natural proteins will be performed.

Phase Two: Research objectives by year

(10³ won)

· In order to understand hydrogen-bonding dynamics and its effects on various peptide vibrational (both 1D and 2D) spectra, we will carry out several molecular dynamics simulations of N-methylacetamide in various protic solvents, dipeptide (acetylproline) in an aqueous solution, and a-helical polyalanine in water.

· As the chain length of a given polypeptide increases, there will be systematic trends on the peptide vibrational properties, such as vibrational coupling constants, frequencies, reduced masses, delocalization, and excitonic dynamics.

In Sec.5, we will present much more detailed discussions on these research subjects and methods.

C. Criterion and viewpoint that P.I. offers for research evaluation

* Research results will be published as papers.