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STUDY OF PROTEIN THREE-DIMENSIONAL STRUCTURE AND DYNAMICS USING PEPTIDE AMIDE HYDROGEN/DEUTERIUM EXCHANGE MASS SPECTROMETRY (DXMS) AND CHEMICAL CROSS-LINKING WITH MASS SPECTROMETRY TO CONSTRAIN MOLECULAR MODELING
INTRODUCTION
As more genomes are fully sequenced, there is a shift in interest to explore the intricate interplay of proteins in complex pathways and to study how protein structures vary in the course of these myriad interactions. While many high-throughput structural genomics programs seek to address these problems, it is apparent that producing structural models of protein complexes and large multidomain proteins using conventional techniques can be a slow process taking many months to years. Size limitations in NMR and the ability of a protein or protein complex to crystallize are the greatest hurdles. These bottlenecks have encouraged research into alternate approaches for structure determination such as mass spectrometry based techniques and examination of chemically cross-linked proteins.
While mass spectrometry has not been traditionally viewed as a structure determination tool, advancements in MS techniques in combination with molecular modeling have opened up an entire new field in high-throughput structure determination. One such approach is enhanced peptide amide hydrogen/deuterium exchange mass spectrometry (DXMS) that focuses on liquid chromatography-mass ...
