Tsong Prize awarded to Taylor Colburn | About | Beckstein Lab

Undergraduate student Taylor Colburn was awarded the 2017 Tsong Prize for Undergraduate Research in the Department of Physics at Arizona State University for his work on Simulating the conformational transitions of the transmembrane symporter Mhp1.

The annual Tsong prize was endowed by Professor Ignatius Tsong to encourage undergraduate research in Physics at ASU.

Abstract

The function of many proteins depends on large-scale conformational changes. Because these conformational transitions are rare events, it is very difficult to investigate them with equilibrium molecular dynamics (MD) simulations, which have otherwise become an important tool to study the molecular mechanisms of macromolecular systems. A variety of techniques — such as the Dynamic IMportance Sampling (DIMS) ¹ method and various elastic network-based approaches have been developed to overcome timescale limitations and produce physically plausible trajectories between putative metastable states. We sought to characterize a number of different path generating and sampling methods, including DIMS with and without an implicit membrane model, by producing multi-directional trajectories of the transmembrane nucleobase symporter Mhp1 ². All trajectories were compared to one another using Root-Mean-Square Distances (RMSDs), structural order-parameters, and Path Similarity Analysis (PSA) ³. In particular, PSA showed that while trajectory generating methods were broadly similar, paths from each method were also clearly distinguishable.

References

1. ^a Perilla JR, Beckstein O, Denning EJ, Woolf TB. Computing ensembles of transitions from stable states: Dynamic importance sampling. J Comput Chem. 2011;32(2):196-209.
2. ^a T. Shimamura, S. Weyand, O. Beckstein, N. G. Rutherford, J. M. Hadden, D. Sharples, M. S. P. Sansom, S. Iwata, P. J. F. Henderson, and A. D. Cameron. Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1. Science, 328(5977):470–473, 2010. doi: 10.1126/ science.1186303.
3. ^a Seyler SL, Kumar A, Thorpe MF, Beckstein O (2015) Path Similarity Analysis: A Method for Quantifying Macromolecular Pathways. PLoS Comput Biol 11 (10): e1004568. doi: 10.1371/journal.pcbi.1004568