Computational Methods for Structural and Functional Studies of Alzheimer's Amyloid Ion Channels

Overview

Journal Methods Mol Biol

Specialty Molecular Biology

Date 2015 Oct 11

PMID 26453217

Citations 4

Authors

Hyunbum Jang

Fernando Teran Arce

Joon Lee

Alan L Gillman

Srinivasan Ramachandran

Bruce L Kagan

Ratnesh Lal

Ruth Nussinov

Affiliations

Soon will be listed here.

Abstract

Aggregation can be studied by a range of methods, experimental and computational. Aggregates form in solution, across solid surfaces, and on and in the membrane, where they may assemble into unregulated leaking ion channels. Experimental probes of ion channel conformations and dynamics are challenging. Atomistic molecular dynamics (MD) simulations are capable of providing insight into structural details of amyloid ion channels in the membrane at a resolution not achievable experimentally. Since data suggest that late stage Alzheimer's disease involves formation of toxic ion channels, MD simulations have been used aiming to gain insight into the channel shapes, morphologies, pore dimensions, conformational heterogeneity, and activity. These can be exploited for drug discovery. Here we describe computational methods to model amyloid ion channels containing the β-sheet motif at atomic scale and to calculate toxic pore activity in the membrane.

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