[Gone]推荐审稿 - 未名空间MITBBS历史存档

国际科技财经博客移民网络热点娱乐民生时事公众号

Redian新闻

>未名空间

>Immigration - 落地生根

[Gone]推荐审稿

[Gone]推荐审稿# Immigration - 落地生根

x*j2013-07-23 07:07

1 楼

省得自己根本不用或者不敢用在乱点，不如把机会让给需要的人。

d*52013-07-23 07:07

2 楼

Journal of Biomolecular Structure & Dynamics
TITLE: Understanding the interaction determinants of CAPN1 inhibition by
CAST4 from bovines: insights from molecular modeling
ABSTRACT:
The activated mammalian CAPN-structures, the CAPN/CAST complex in particular
, have become an invaluable target model using the structure-based virtual
screening of drug candidates from discovery phase to development for over-
activated CAPN linked to several diseases such as post-ischemic injury and
cataract formation. It was proposed that the effect of Ca+2-binding to the
enzyme included activation as well as the dissociation, aggregation, and
autolysis of the small regular subunits. This enzyme aggregation is also
known not only to decrease known inhibitor efficiency, but also to elicit
excessive immunological response. The large, catalytic subunit aggregation
of CAPN would be expected to promote aqueous-exposed hydrophobic
dimerization surface even in domain DIV even in the absence of Ca+2,
energetically unfavorable. These effects lead to formation of randomly
associated aggregates, as a result of Ca+2-induced conformational
rearrangement and partial dissociation. Therefore, we have minutely scanning
from the inhibitor's functional sites to interaction determinants in the
sites by our predicted model structures of CAPN1, along with its activity
states and complex with CAST4 from bovines. Furthermore, we predicted
mutational effects associated with human disease of LGMA-2A on protein
stability, binding affinity and aggregation in the bovine CAPN1/CAST4
complex. These results suggest that the more distinct interaction
preferences of the bovine CAPN regulation system, compared to other CAPN
family members, were principally related to the trace residues for enzyme
activation and inhibition by CAST4. We point out the importance of trace
residues from bovine for screening the potential development targeting sites
to discovery small inhibitors.
有兴趣的请发简历到我的邮箱 l***[email protected] 如果合适的我会推荐一下。