科研之友
微信
新浪微博
Facebook
分享链接
摘要
The physiological role of human cystatin C (HCC) in the brain of individuals suffering from Alzheimer's disease (AD) is currently an uncertainty in the scientific community. The protein complex interface between HCC and amyloid beta (A beta), an aggregated protein in the AD brain, is of great interest due to the potential roles of HCC as an agonist and/or antagonist in AD progression. Thus, to understand the molecular details of HCC-A beta interactions, all-atom molecular dynamic simulations were performed in explicit water under physiological conditions. Rigid body protein-protein docking was utilized to obtain the best modes of interactions between A beta and HCC by using energy functions that comprise pairwise shape complementarity with desolvation and electrostatics. Subsequently, two top docking structures were simulated and evaluated for molecular interactions. A detailed trajectory analysis indicates favorable binding conformations between A beta and HCC where A beta goes through major conformational rearrangements while HCC retains its major secondary structures throughout the simulations. Root mean square deviation, radius of gyration and solvent accessible surface area analyses also suggest a larger conformational sampling for A beta in comparison to HCC. Moreover, hydrogen bonding and hydrophobic interactions were found to have important roles in the stability of complexes between A beta and HCC. Overall, the results obtained from this study provide molecular insight into the interaction pathways of A beta and HCC and emphasize the importance of noncovalent forces in biomolecular interactions of therapeutic significance.
- 出版日期2018-2
