About the Lab

The projects in Ma's Laboratory focus at the frontier of modern computational biophysics and structural biology. This includes three major research directions.

Multi-Resolution and Multi-Length Scale Simulation of Supramolecular Complexes

Large-scale conformational transitions in protein structures play an important role in a variety of cellular processes. Understanding such transitions is one of the central tasks of modern biophysics and structural biology. Among all the available structural and biophysical methods, computer simulation is a powerful method in modeling the motions of proteins in atomic detail.

These research projects primarily focus on systems that involve coordinated large-domain movements. Recent work on the molecular chaperonin GroEL and F1-ATPase has provided paradigms for this type of research. It also demonstrates that molecular dynamics simulation has come into an age of realistically modeling very large protein complexes.

Structural Refinement for X-Ray, Cryo-EM and Fiber Diffraction

In recent history, molecular dynamics simulation has been successfully employed to significantly improve the structure refinement in x-ray crystallography. However, as structural biology moves toward meeting the new challenges imposed by the study of more complex and more dynamic biological systems, more advanced computational methods are urgently needed to effectively deal with molecular motions in structure refinement.

Ma’s group is committed to improving structure refinement in x-ray crystallography, electron cryomicroscopy (cryo-EM) and fiber diffraction. Quantized elastic deformational model (QEDM) has been demonstrated highly effective in assisting cryo-EM single-particle reconstruction of intrinsically flexible biological systems. Substructure synthesis method (SSM) is extremely powerful for enhancing the structure refinement against fiber diffraction data. Moreover, important progress of improving x-ray structure refinement has been recently achieved. These lines of research will undoubtedly provide powerful tools for structure refinement in the wider fields of structural biology.

Structure Modeling and Prediction

With the advance of cryo-EM single-particle reconstruction, more and more intermediate-resolution structures are available. It would be extremely useful if protein secondary structures and protein topology could be determined from intermediate-resolution data.

Ma’s group has recently developed sheetminer and sheettracer that are capable of accurately locating beta-sheets and building beta-strands in intermediate-resolution density maps. Once protein secondary structures are in place, protein topology can be determined using approaches developed in our group. These methods will greatly enhance the ability to obtain meaningful information about protein structure and function from intermediate-resolution data.