Molecular complexes conformational analysis

Structure determination of a Galectin-3-carbohydrate complex. Conformational analysis of partially folded proteins illustrated by application to the molecular recognition element of Sendai virus nucleoprotein. ... 

When a validated hit is selected as a promising lead compound, its physicochemical profile must be studied in detail. Sophisticated in silica approaches such as 3D lipophilicity predictions coupled with extensive conformational analysis [49, 50,135,146] and molecular field interactions (MIFs) [147-150] could be helpful to better interpret the detailed experimental investigations of their ionization constants by capillary electrophoresis or potentiometric titrations [151, 152] and their lipophilicity profiles by potentiometry [153]. However, these complex approaches cannot be performed easily on large number of compounds and are generally applied only on the most promising compounds. 

A review of the Journal of Physical Chemistry A, volume 110, issues 6 and 7, reveals that computational chemistry plays a major or supporting role in the majority of papers. Computational tools include use of large Gaussian basis sets and density functional theory, molecular mechanics, and molecular dynamics. There were quantum chemistry studies of complex reaction schemes to create detailed reaction potential energy surfaces/maps, molecular mechanics and molecular dynamics studies of larger chemical systems, and conformational analysis studies. Spectroscopic methods included photoelectron spectroscopy, microwave spectroscopy circular dichroism, IR, UV-vis, EPR, ENDOR, and ENDOR induced EPR. The kinetics papers focused on elucidation of complex mechanisms and potential energy reaction coordinate surfaces. 

A combination of the two techniques was shown to be a useful method for the determination of solution structures of weakly coupled dicopper(II) complexes (Fig. 9.4)[119]. The MM-EPR approach involves a conformational analysis of the dimeric structure, the simulation of the EPR spectrum with the geometric parameters resulting from the calculated structures and spin hamiltonian parameters derived from similar complexes, and the refinement of the structure by successive molecular mechanics calculation and EPR simulation cycles. This method was successfully tested with two dinuclear complexes with known X-ray structures and applied to the determination of a copper(II) dimer with unknown structure (Fig. 9.5 and Table 9.9)[119]. 

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