A computational examination of the binding interactions of amyloidβ and human cystatin C

Author:

Sharma Arun K.1ORCID,Persichetti Joseph1,Tale Ermin1,Prelvukaj Gent1,Cropley Tyler1,Choudhury Rajib2

Affiliation:

1. Department of Chemistry and Physics, Wagner College, Staten Island, New York, USA

2. Department of Physical Sciences, Arkansas Tech University, Russellville, Arkansas, USA

Abstract

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[Formula: see text] (A[Formula: see text]), 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[Formula: see text] 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[Formula: see text] 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[Formula: see text] and HCC where A[Formula: see text] 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[Formula: see text] in comparison to HCC. Moreover, hydrogen bonding and hydrophobic interactions were found to have important roles in the stability of complexes between A[Formula: see text] and HCC. Overall, the results obtained from this study provide molecular insight into the interaction pathways of A[Formula: see text] and HCC and emphasize the importance of noncovalent forces in biomolecular interactions of therapeutic significance.

Publisher

World Scientific Pub Co Pte Lt

Subject

Computational Theory and Mathematics,Physical and Theoretical Chemistry,Computer Science Applications

Cited by 6 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3