US EPA

520742 

Journal Article 

Probing protein aggregation using discrete molecular dynamics 

Sharma, S; Ding, F; Dokholyan, NV 

2008 

Yes 

Frontiers in Bioscience
ISSN: 1093-9946
EISSN: 1093-4715 

13 

4795-4807 

English 

10.2741/3039 

Understanding the role of biomolecular dynamics in cellular processes leading to human diseases and the ability to rationally manipulate these processes is of fundamental importance in scientific research. The last decade has witnessed significant progress in probing biophysical behavior of proteins. However, we are still limited in understanding how changes in protein dynamics and inter-protein interactions occurring in short length- and time-scales lead to aberrations in their biological function. Bridging this gap in biology probed using computer simulations marks a challenging frontier in computational biology. Here we examine hypothesis-driven simplified protein models in conjunction with discrete molecular dynamics in the study protein aggregations, implicated in series of neurodegenerative diseases, such as Alzheimer's and Huntington's diseases. Discrete molecular dynamics simulations of simplified protein models have emerged as a powerful methodology with its ability to bridge the gap in time and length scales from protein dynamics to aggregation, and provide an indispensable tool for probing protein aggregation. 

protein aggregation; protein misfolding; simplified Modeling; aggregation kinetics; folding thermodynamics; discrete molecular; dynamics; molecular dynamics; computational biology; biophysics; MD; DMD; misfolding; molecular dynamics; amyotrophic-lateral-sclerosis; 3-helix bundle protein; alpha-helix; in-silico; neurodegenerative diseases; folding thermodynamics; superoxide-dismutase; computer-simulation; amyloid formation; free-energy